Strong Background Signal Research Articles

Rendering graphene supports hydrophilic with non-covalent aromatic functionalization for transmission electron microscopy

Amorphous carbon films have been routinely used to enhance the preparation of frozen-hydrated samples for transmission electron microscopy (TEM), either in retaining protein concentration, providing mechanical stability or dissipating sample charge. However, strong background signal from the amorphous carbon support obstructs that of the sample, and the insulating properties of thin amorphous carbon films preclude any efficiency in dispersing charge. Graphene addresses the limitations of amorphous carbon. Graphene is a crystalline material with virtually no phase or amplitude contrast and unparalleled, high electrical carrier mobility. However, the hydrophobic properties of graphene have prevented its routine application in Cryo-TEM. This Letter reports a method for rendering graphene TEM supports hydrophilic—a convenient approach maintaining graphene's structural and electrical properties based on non-covalent, aromatic functionalization.

Signal Processing for the Measurement of the Deuterium/Hydrogen Ratio in the Local Interstellar Medium

We report on a comprehensive signal processing procedure for very low signal levels for the measurement of neutral deuterium in the local interstellar medium from a spacecraft in Earth orbit. The deuterium measurements were performed with the IBEX-Lo camera on NASA’s Interstellar Boundary Explorer (IBEX) satellite. Our analysis technique for these data consists of creating a mass relation in three-dimensional time of flight space to accurately determine the position of the predicted D events, to precisely model the tail of the H events in the region where the H tail events are near the expected D events, and then to separate the H tail from the observations to extract the very faint D signal. This interstellar D signal, which is expected to be a few counts per year, is extracted from a strong terrestrial background signal, consisting of sputter products from the sensor’s conversion surface. As reference we accurately measure the terrestrial D/H ratio in these sputtered products and then discriminate this terrestrial background source. During the three years of the mission time when the deuterium signal was visible to IBEX, the observation geometry and orbit allowed for a total observation time of 115.3 days. Because of the spinning of the spacecraft and the stepping through eight energy channels the actual observing time of the interstellar wind was only 1.44 days. With the optimised data analysis we found three counts that could be attributed to interstellar deuterium. These results update our earlier work.

A Feature Extraction Method of Gear Fault Based on the SVD EMD and Morphology

In order to extract the weak signal from strong background signal characteristics, a feature extraction method combined of the singular value decomposition (SVD), empirical mode decomposition (EMD) and mathematical morphology was proposed. The signal got through the singular value decomposition first. Next took the average value of the decomposed main components. And carried on the empirical mode decomposition and selected the main component to summate and refactor. Then morphological difference filter was used to extract the frequency characteristics of the fault signal. The results of numerical simulation test and gear fault simulation experiments show that the proposed method can clearly extract the frequency characteristics of weak signal from strong background signal and noise. Comparison has been done with the results of singular value decomposition (SVD) and morphological filtering method and empirical mode decomposition form of filtering method. It proves the effectiveness of the proposed method.

Evidence of direct detection of interstellar deuterium in the local interstellar medium by IBEX

We report the first in situ measurements of neutral deuterium originating in the local interstellar medium (LISM) in Earth’s orbit. These measurements were performed with the IBEX-Lo camera on NASA’s interstellar boundary explorer (IBEX) satellite. All data from the spring observation periods of 2009 through 2011 have been analysed. In the three years of the IBEX mission time, the observation geometry and orbit allowed for a total observation time of 115.3 days for the LISM. However, the effects of the spinning spacecraft and the stepping through 8 energy channels mean that we are only observing the interstellar wind for a total time of 1.44 days, in which 2 counts for interstellar deuterium were collected. We report here a conservative number, because a possibility of systematic error or additional noise, though eliminated in our analysis to the best of our knowledge, only supports detection at a 1-sigma level. From these observations, we derive a ratio D/H = � 5.8 ± 4.4 � × 10 −4 at 1 AU. After modelling the transport and loss of D and H from the termination shock to Earth’s orbit, we find that our result of D/HLISM = � 1.6 ± 1.2 � × 10 −5 agrees with D/HLIC = � 1.6 ± 0.4 � × 10 −5 for the local interstellar cloud. This weak interstellar signal is extracted from a strong terrestrial background signal consisting of sputter products from the sensor’s conversion surface. As reference, we accurately measure the terrestrial D/H ratio in these sputtered products and then discriminate this terrestrial background source. Because of the diminishing D and H signal at Earth’s orbit during the rising solar activity due to photoionisation losses and increased photon pressure, our result demonstrates that in situ measurements of interstellar deuterium in the inner heliosphere are only possible during solar minimum conditions.

Optimisation of wavelength modulated Raman spectroscopy: towards high throughput cell screening.

In the field of biomedicine, Raman spectroscopy is a powerful technique to discriminate between normal and cancerous cells. However the strong background signal from the sample and the instrumentation affects the efficiency of this discrimination technique. Wavelength Modulated Raman spectroscopy (WMRS) may suppress the background from the Raman spectra. In this study we demonstrate a systematic approach for optimizing the various parameters of WMRS to achieve a reduction in the acquisition time for potential applications such as higher throughput cell screening. The Signal to Noise Ratio (SNR) of the Raman bands depends on the modulation amplitude, time constant and total acquisition time. It was observed that the sampling rate does not influence the signal to noise ratio of the Raman bands if three or more wavelengths are sampled. With these optimised WMRS parameters, we increased the throughput in the binary classification of normal human urothelial cells and bladder cancer cells by reducing the total acquisition time to 6 s which is significantly lower in comparison to previous acquisition times required for the discrimination between similar cell types.

Nuclear spin singlet states as a contrast mechanism for NMR spectroscopy

Nuclear magnetic resonance (NMR) spectra of complex chemical mixtures often contain unresolved or hidden spectral components, especially when strong background signals overlap weaker peaks. In this article we demonstrate a quantum filter utilizing nuclear spin singlet states, which allows undesired NMR spectral background to be removed and target spectral peaks to be uncovered. The quantum filter is implemented by creating a nuclear spin singlet state with spin quantum numbers j = 0, mz = 0 in a target molecule, applying a continuous RF field to both preserve the singlet state and saturate the magnetization of undesired molecules and then mapping the target molecule singlet state back into an NMR observable state so that its spectrum can be read out unambiguously. The preparation of the target singlet state can be carefully controlled with pulse sequence parameters, so that spectral contrast can be achieved between molecules with very similar structures. We name this NMR contrast mechanism 'Suppression of Undesired Chemicals using Contrast-Enhancing Singlet States' (SUCCESS) and we demonstrate it in vitro for three target molecules relevant to neuroscience: aspartate, threonine and glutamine.

Magnetomotive photoacoustic imaging: in vitro studies of magnetic trapping with simultaneous photoacoustic detection of rare circulating tumor cells.

Photoacoustic (PA) imaging has been demonstrated to be a promising modality in molecular imaging for detection of nanoparticle-targeted diseased cells or tissues. However, intrinsic absorbers, such as blood, produce strong PA background signals that severely degrade the detection sensitivity and specificity of targeted objects. Magnetomotive photoacoustic (mmPA) imaging, a newly developed molecular imaging modality, introduced dynamic manipulation into traditional PA imaging. Unlike conventional PA imaging, magnetomotive manipulation with simultaneous ultrasound/PA imaging of agents incorporating magnetic nanoparticles enables direct visualization of the signal generating object and can dramatically reduce background signals from strong optical absorbers. This paper briefly reviews recent developments in mmPA imaging, including uses of composite contrast agent, design of magnet system, and data processing for motion filtering. The use of mmPA imaging in detecting rare circulating tumor cells in blood vessels, which remains a big challenge for real-time in vivo examination using current methodologies, was also addressed.

Detection and quantification of steady-state ethylene oxide formation over an Ag(1 1 1) single crystal

Extensive experiments with a flow reactor were performed to reliably detect the steady-state catalytic formation of ethylene oxide from ethylene and oxygen on an Ag(111) single crystal. For single crystals with their small surfaces, this had been a major experimental problem because of the low reaction probability of ethylene and cross-sensitivities in the mass spectra. Using 16O2 ethylene oxide could be detected on mass fragment m/z=43, using 18O2 on m/z=31 and m/z=45, but strong time-dependent background signals had to be subtracted. This was achieved by periodic temperature changes of the reactor. After proper inclusion of all effects, a mole fraction of ethylene oxide of only 3×10−5 with respect to the reaction gas mixture, which was unequivocally produced by catalysis on the Ag sample, could be determined with a signal-to-noise ratio of more than one order of magnitude above the detection limit.

In Vivo Blood Glucose Quantification Using Raman Spectroscopy

We here propose a novel Raman spectroscopy method that permits the noninvasive measurement of blood glucose concentration. To reduce the effects of the strong background signals produced by surrounding tissue and to obtain the fingerprint Raman lines formed by blood analytes, a laser was focused on the blood in vessels in the skin. The Raman spectra were collected transcutaneously. Characteristic peaks of glucose (1125 cm-1) and hemoglobin (1549 cm-1) were observed. Hemoglobin concentration served as an internal standard, and the ratio of the peaks that appeared at 1125 cm-1 and 1549 cm-1 peaks was used to calculate the concentration of blood glucose. We studied three mouse subjects whose blood glucose levels became elevated over a period of 2 hours using a glucose test assay. During the test, 25 Raman spectra were collected transcutaneously and glucose reference values were provided by a blood glucose meter. Results clearly showed the relationship between Raman intensity and concentration. The release curves were approximately linear with a correlation coefficient of 0.91. This noninvasive methodology may be useful for the study of blood glucose in vivo.

PCEST: Positive contrast using Chemical Exchange Saturation Transfer

Chemical Exchange Saturation Transfer (CEST) contrast utilizes selective pre-saturation of a small pool of exchanging protons and subsequent detection of the decrease in bulk water signal. The CEST contrast is negative and requires detection of small signal change in the presence of a strong background signal. Here we develop a Positive CEST (pCEST) detection scheme utilizing the analogous nature of the CEST and off-resonance T1ρ experiments and exploring increased apparent relaxation rates in the presence of the selective pre-saturation. pCEST leads to the positive contrast, i.e., increased signal intensity as the result of the presence of the agent and RF pre-saturation. Simultaneously substantial background suppression is achieved. The contrast can be switched “ON” and “OFF”, similar to the original CEST.

Binding of benzodiazepine drugs to bovine serum albumin: A second derivative spectrophotometric study

The binding constants ( K values) of three benzodiazepine drugs to bovine serum albumin were determined by a second derivative spectrophotometric method. Despite the sample and reference samples were prepared in the same way to maintain the same albumin content in each sample and reference pair, the absorption spectra show that the baseline compensation was incomplete because of the strong background signals caused by bovine serum albumin. Accordingly, further quantitative spectral information could not be obtained from these absorption spectra. On the other hand, the calculated second derivative spectra clearly show isosbestic points indicating the complete removal of the residual background signal effects. Using the derivative intensity differences (Δ D values) of the studied benzodiazepine drugs before and after the addition of albumin, the binding constants were calculated and obtained with R.S.D. of less than 8%. The interactions of drugs with bovine serum albumin were investigated using Scatchard's plot. In addition, the consistency between the fractions of bound benzodiazepine calculated from the obtained K values and the experimental values were established. The results indicate that the second derivative method can be advantageously applicable to the determination of binding constants of drugs to serum albumin without prior separation. Moreover, the validity of the proposed method was confirmed.

Fault Diagnosis of Wet-Shift Clutch Based on STFT and Wavelet

The paper analyzes the failure mechanism of the wet shifting clutch, and puts forward the concept that the deformation of the clutch friction plate leads to the irregular collision between the driving and driven sides of disengaged clutch and accordingly forms the transient pulse signal; the short-time Fourier analysis on the vibration signals of failed clutch obtained via test proves such concept. The transient pulse signal in the relatively strong background signal is clearly extracted through the wavelet decomposition after zero setting, and an efficient wet shifting clutch fault diagnosis method is hereby formed.

PH‐Activated Near‐Infrared Fluorescence Nanoprobe Imaging Tumors by Sensing the Acidic Microenvironment

AbstractImaging tumors in their early stages is crucial to increase the surviving rate of cancer patients. Currently most fluorescence probes visualize the neoplasia by targeting the tumor‐associated receptor over‐expressed on the cancer cell membrane. However, the expression level of these receptors in vivo is hard to predict, which limits their clinical translation. Furthermore, the signal output of these receptor‐targeting probes usually stays at a high level, which leads to a strong background signal in normal tissue due to non‐specific binding. In contrast to receptors, characteristics of the tumor microenvironment – such as acidosis – are pervasive in almost all solid tumors and can be easily accessed. In this work, a novel biodegradable nanoprobe InNP1 that demonstrates pH‐activated near‐infrared (NIR) fluorescence in both human glioblastoma U87MG cancer cells in vitro and the subcutaneous U87MG tumor xenografts in vivo is developed. Bio‐distribution, in vivo optical imaging, and autoradiography studies demonstrate that the pH‐activated NIR fluorescence is the dominant factor responsible for the high tumor/normal tissue (T/N) ratio of InNP1 in vivo. Overall, the work provides a nanoprobe prototype to visualize the solid tumor in vivo with high sensitivity and minimal systemic toxicity by sensing the tumor acidic microenvironment.

Diterpenoic Acids Analysis Using a Coupled TLC-Surface-Enhanced Raman Spectroscopy System

Hyphenation of thin layer chromatography (TLC) with surface-based spectral methods requires a homogeneous surface for direct and quantitative analysis on the chromatographic plate after separation. Since most chromatographic materials do not produce strong background signals in Raman spectroscopy (RS) or surface-enhanced RS (SERS), we tested the suitability of two different chromatographic substrates and one interface for coupling SERS with TLC. This was carried out by using a chromatographic thin layer, specially produced for RS measurements, and a monolithic silica thin layer. A typical TLC plate with a modified aluminium backplate foil on one side was used as an interface. Three biologically active diterpenes, namely gibberellic acid (GA), abietic acid (AA) and kaurenoic acid (KA), were used as test analytes. Stock solutions were applied directly onto the surface, followed by the addition of silver colloid and measurements were taken by SERS. The strongest signal (excitation at 514.5 nm) was obtained for GA using a Raman treated thin layer where the enhancement factor value was determined to be 102. Several fundamental Raman bands for GA were found at 1622, 1593, 1570, 1542, 1366 and 1236 cm−1. When the monolithic silica layer was used, no useful SERS signals were observed. The SERS spectra on modified aluminium backplate for AA and GA were quite similar and no SERS spectrum was obtained for KA. Future research will be concerned towards the use of nanostructured surfaces for SERS analysis.

Tip-substrate interaction in optical near-field microscopy

We study the tip-substrate interaction in apertureless scanning near-field optical microscopy (aSNOM) with a three-dimensional model of both near and far fields. Starting from the analytically well understood two-sphere model, we obtain a realistic tip-substrate model by continuous deformation of the upper sphere into an elongated conical tip several wavelengths long with a hemispherical apex radius of just a few nanometers. The other sphere is enlarged to represent a locally flat substrate surface below the tip apex. This adiabatic transition toward the final system helps us to understand the origin of the different contributions. We find that dielectric tips, in spite of the absence of plasmonic resonances, are quite suitable for aSNOM. This is supported by experimental results. Working with the sharpest commercially available Si tips holds promise for pushing the routinely achievable lateral resolution down to the sub-10-nm range. At $1\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ tip-substrate distance, we obtain local-field enhancements of many tens. The instantaneous, elastically backscattered intensity is calculated for variable tip-substrate distances to study demodulation at higher harmonics of an oscillating probe. We confirm that the local optical information is discriminated even against strong background signals, provided the vibration amplitude is kept small. However, this discrimination scheme is rather sensitive to crosstalk from anharmonic motion and care must be exercised in choosing appropriate experimental parameters to achieve reliable optical contrast.

Focus-engineered coherent anti-Stokes Raman scattering microscopy: a numerical investigation

The coherent anti-Stokes Raman scattering (CARS) signal is calculated as a function of focal-field distributions with engineered phase jumps. We show that the focal fields in CARS microscopy can be shaped such that the signal from the bulk is suppressed in the forward detection mode. We present the field distributions that display enhanced sensitivity to vibrationally resonant object interfaces in the lateral dimension. The use of focus-engineered CARS provides a simple means to detect chemical edges against the strong background signals from the bulk.

Optical scanning instrument for ultrafast pump-probe spectroscopy of biomolecules at cryogenic temperatures

We demonstrate novel optical scanning and detection instrumentation that is particularly useful for the interrogation of stationary cryogenic samples in pump-probe spectroscopy. The technique uses a spinning lens to scan multiple laser beams over a stationary sample while maintaining the focal properties of the beams. This significantly lengthens the time window for the sample reset to equilibrium and improves the photostability of stationary samples. In addition, we describe a signal processing methodology that discriminates against the strong background signal that can arise from leakage of the pump laser pulse train into the detector. These techniques are particularly useful in pump-probe studies of ultrafast processes in biological systems where sample deterioration, pump induced thermal lensing, and light scattering into the detection channel (e.g., induced by light scattering from a cryogenic matrix) are problematic. Generally, the optical scanning and detection instrumentation described here enable the study of a variety of biological systems, without the need for intricate spinning or flowing sample containers, making it possible to perform ultrafast pump-probe experiments on stationary samples such as a cryogenic matrix.

Matrix-free Laser Desorption/Ionization on Vertically Aligned Carbon Nanotube Arrays

The matrix-assisted laser desorption/ionization (MALDI) has established its position as one of the most useful ionization techniques in mass spectrometry and its contribution to the scientific communities related to mass spectrometry was appreciated with the 2002 Nobel Prize in Chemistry given to the first developer, Tanaka. It is really an effective and sensitive ion formation technique which commonly employs an organic acid as the matrix. The use of such organic acids as the matrices has provided the high efficiency of desorption and ionization of large molecules including peptides, proteins, synthetic polymers, etc. for the MALDI technique. Interestingly, the matrix, which made the MALDI technique practical, poses an intrinsic constraint to the analyses of relatively small molecules below 1000 Da because the low mass regions in MALDI mass spectra are dominated by the strong background signals of the matrix molecule, its dimer, and their clusters with solvent molecules. Several approaches have been tried to find the methods that give the high desorption/ionization efficiency of MALDI without using the organic matrices. Probably the most successful matrix-free laser desorption/ ionization technique must be the use of porous silicon as a replacement of the matrix. The desorption/ionization on porous silicon(abbreviated as DIOS) was found to be highly sensitive for the sample below 3,000 Da and showed no interference at all in this low mass region, and is now commercially available. Although the DIOS has been very successful, it has a non-negligible shortcoming that its performance deteriorates with time after fabrication. The degradation may be slowed down by derivatization of the surface but cannot be completely eliminated. In this Note, we report that the vertically grown carbon nanotube arrays may be used as a substrate for matrix-free laser desorption/ionization of relatively small molecules. It turned out to be highly sensitive for small peptides near and below 2,000 Da and its ionization efficiency does not change after a long-time storage in the room atmosphere.

Induction of thymine dimers by solar radiation in natural freshwater phytoplankton assemblages in Patagonia, Argentina

Natural phytoplankton assemblages from a freshwater lake in Trelew (Province of Chubut, Patagonia, Argentina) were exposed to natural solar radiation at different depths in a water basin filled with fresh water rich in humic substances. Samples were taken at regular intervals for DNA extraction and subsequent analysis of DNA damage by determining the formation of thymine dimers using an immuno-dot-blot procedure. The use of a colorimetric detection system based on the reaction of alkaline phosphatase with BCIP (5-bromo-4-chloro-3-indolyl phosphate)/NBT (nitro blue tetrazolium) proved unsatisfactory because of uneven and strong background signals. As a consequence the antibodies were stripped and the blots were reprobed successfully, using a chemoluminescence based detection system. Natural solar radiation caused an increase from 3.2 ± 0.9 thymine dimers (T^T) per mega base pair (Mbp) to 50.9 ± 3.8 T^T Mbp−1 during the light period in natural phytoplankton exposed at the surface. When the UV-B component of the solar radiation was removed by a 320 nm cut-off filter, no thymine dimers were produced. After prolonged exposure at the surface, some but not total recovery occurred overnight. There was no significant DNA damage in the samples exposed at 85 cm depth (kd = 3.62 m−1 at 305 nm). The results indicate that the impinging UV-B radiation at the study site may be deleterious to the survival of phytoplankton exposed at the water surface and thus significantly alter the nutrient cycling and biomass production.

Vibrational sum-frequency observation of synthetic diamonds

Sum-frequency generation (SFG) spectroscopy was applied to the study of plasma hydrogenated diamond C(100) surface of a synthetic diamond. Two vibrational resonance peaks with the intensities strongly dependent on the polarization combinations of the visible and infrared beams were observed at 2899 and 2924 cm −1. From the results of SFG measurements for various polarization combinations, the 2899 and 2924 cm −1 peaks were assigned, respectively, to the antisymmetric and symmetric CH stretching modes of HCCH group on H/C(100)-2×1 surface. In addition, a strong background signal with an oscillatory profile was observed.