Seconds Of Sampling Research Articles

Exploring the potential of branched submicron channels-based structures in ultra-thin Ag films for SERS molecular sensing

Noble metal-based nanostructures are actively studied due to their promising prospects for fabricating efficient substrates for Surface Enhanced Raman Spectroscopy (SERS)-based molecular sensing. In this work, we report the gross potential of SERS substrates based on branched submicron channels in ultra-thin Ag films. These films were fabricated by magnetron sputtering and then annealed in high vacuum conditions to induce branched channels growth by thermal dewetting. Different sets of nominally equal samples were tested during a determined period of time, using confocal Raman spectroscopy and methylene blue (MB) as Raman-active molecule, to assess their performance for SERS in ambient aging conditions. Micro-Raman intensity mapping studies demonstrated the emergence of “hot spots” enhancing the Raman signal in the branched submicron channels. A good mass sensitivity and fast spectral acquisition were achieved using these nanostructures, observing an exceptional spectral resolution and identifying all main vibrational states of MB in a few seconds for samples with a MB surface mass density of about 2 ng/mm2. A good spectral resolution was achieved even using shorter measurement times from 1.00 to 0.05 s, suggesting the potential for fast SERS determinations. Samples showed good reproducibility in the Raman spectral response during the tested period, demonstrating the marginal impact of the aging effects on the Raman signal enhancement and ensuring a time-stable SERS performance in the short term. Our results show that the proposed nanostructures are promising candidates for the development of substrates with competitive-sensitivity, time-stability, and fast SERS response, representing a simple and attractive alternative for efficient SERS-based molecular sensing.

Rapid sampling during synthesis of lead halide perovskite nanocrystals for spectroscopic measurement

The photophysical properties of lead halide perovskite nanocrystals (NCs) are critical to their potential application in light emitting devices and other optoelectronics, and are typically characterized using optical spectroscopies. Measurements of nuclei and nascent NC photophysics during synthesis provide insight into how the reaction can be changed to control the properties of the resulting NCs. However, these measurements are typically only performed ex situ after growth is halted by centrifuging the reaction mixture for several minutes. Here, a method is reported to rapidly sample the reaction mixture during a solvation-limited synthesis to enable multiple spectroscopic measurements during nucleation and NC growth. Absorbance and fluorescence measurements of a reaction mixture during the formation of methylammonium lead triiodide perovskite NCs are reported. The changing positions of spectral features as a function of reaction time show the expected weakening of exciton confinement during NC growth. The evolving fluorescence spectra demonstrate that the capping and surface passivation of nascent NCs changes during the reaction. The species in the reaction mixture, particularly during the early stages of the synthesis, are shown to be unstable. This indicates that, even for a relatively slow solvation-limited reaction, the photophysics of the reaction mixture can only be accurately captured if spectroscopic measurements are completed within seconds of sampling. The common use of centrifugation to quench NC syntheses prior to spectroscopic measurement biases the NC population towards more stable, well-capped NCs and does not accurately report on the full NC population in a reaction mixture.

Abstract 4118: Rapid, non-subjective characterization of disease in preclinical cancer research using desorption electrospray ionization mass spectrometry

Abstract Cancer tissue smears are routinely used in rapid intraoperative pathology workflows using quick staining methods to characterize cancer in surgical margin assessments or tumor pathology. Mass spectrometry (MS) is a sensitive analytic platform that can detect the presence of cancer from the pattern of cancer-specific molecules present in the mass spectrum of the tissue under examination. In particular, mass spectrometry analysis with desorption electrospray ionization (DESI-MS) is shown to have utility in research models for cancer characterization or even for grading different subclasses of disease based on tumor-specific small molecule lipid or metabolites. DESI does not require extensive tissue preparation, and the data collection and analysis can be done within a few seconds. In this work, we evaluate the combination of rapid DESI-MS detection with rapid tissue smear preparation for research use in preclinical xenograft models of breast cancer and pediatric medulloblastoma requiring only seconds of sampling, and an overall preparation and analysis time of less than one minute. Principal component analysis (PCA) was performed to evaluate the concordance between DESI-MS profiles of breast cancer from tissue slices and smears prepared on various surfaces. PCA suggested no statistical discrimination between DESI-MS profiles of tissue sections and tissue smears prepared on glass, polytetrafluoroethylene (PTFE), and porous PTFE. However, the abundances of cancer biomarker ions varied between sections and smears, with DESI-MS analysis of tissue sections yielding higher ion abundances of cancer biomarkers compared with smears. The coefficient of variance (CV) analysis suggests DESI-MS profiles from tissue smears are as reproducible as the ones from tissue sections. The limit of detection with smear samples from single pixel analysis is comparable to tissue sections that average the signal from a tissue area of 0.01 mm2. The smears prepared on the PTFE surface possessed a higher degree of homogeneity compared with the smears prepared on the glass surface. This allowed single MS scans (~1 s) from random positions across the surface of the smear to be used in rapid cancer typing with good reproducibility, providing useful pathologic information at speeds suitable for research use. Likewise, DESI-MS enabled the rapid classification of subgroups of medulloblastoma in these preclinical models. Citation Format: Michael Woolman, Alessandra Tata, Isabelle Ferry, Claudia Kuzan-Fischer, Megan Wu, Sunit Das, Michael D. Taylor, James T. Rutka, Howard J. Ginsberg, Arash Zarrine-Afsar. Rapid, non-subjective characterization of disease in preclinical cancer research using desorption electrospray ionization mass spectrometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4118.

Abstract 741: Rapid detection of necrosis in breast cancer with ex vivo and in situ mass spectrometry analysis methods

Abstract Necrosis is a form of cell death that is often associated with highly aggressive forms of cancer, is of prognostic value in treatment planning. Mass Spectrometry (MS) is a highly sensitive analytic platform capable of providing a molecular profile of cancer on the basis of mass to charge (m/z) ratio of tissue constituent molecules. MS analysis of ex vivo tissue slices from metastatic murine xenograft tumors from LM2-4 cell line with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) allowed direct comparisons with histology images to determine the molecular profile of necrotic tissues. The necrotic tissue is characterized by the presence of a ceramide absent from the viable cancer regions. The spatial distribution of this ion fully correlated to necrotic areas from pathology in additional independent tumor samples examined. The same ion was detected from in situ necrotic tissue using tissue aerosols generated by hand-held ablation probes coupled to evaporative ionization interface in only a few seconds of sampling. These developments further establish MS as a novel tool for rapid pathology that is highly complementary to current histology based methods widely used in characterization of cancer in both imaging mode (to provide spatial information on cancer border) and profiling mode (to provide information on cancer type and subtype); all based on unique molecular profile associated with each cancer type and subtype. Current efforts in creating cancer molecular profile libraries will facilitate translation. Citation Format: Arash Zarrine-Afsar, Bindesh Shrestha, Alessandra Tata, Michael Woolman, Manuela Ventura, Nicholas Bernards, Milan Ganguly, Howard Ginsberg, Jinzi Zheng, Emma Bluemke. Rapid detection of necrosis in breast cancer with ex vivo and in situ mass spectrometry analysis methods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 741. doi:10.1158/1538-7445.AM2017-741

Stability of X-band EPR signals from fingernails under vacuum storage

EPR signals of different origin have been tested in human finger- and toe-nails with an X-band EPR technique for different conditions of nail storage. Three different signals were identified, namely a singlet at g = 2.005, a doublet at g = 2.004 with a splitting constant A = 1.8mT, and an anisotropic signal at g1 = 2.057, g2 = 2.029 and g3 = 2.003 (positions of local extrema). All EPR spectra from nails, whether irradiated or mechanically stressed, can be described as a superposition of these three signals. The singlet is responsible for the background signal (BG), is the main component of radiation-induced signals (RIS) for low doses (100Gy or lower) and also contributes to mechanically-induced signals (MIS). This signal is quite stable under vacuum storage, but can be reduced almost to zero by soaking in water. The behavior of this signal under ambient conditions depends on many factors, such as absorbed dose, air humidity, and ambient illumination intensity at the place of storage. The doublet arises after exposure of nails to high (few hundreds Gy and higher) doses or after mechanical stress of samples. Depending on how this signal was obtained, it may have bulk or surface locations with quite different stability properties. The surface-located doublet (generated on the nail edges during cutting or clipping) is quite unstable and decays over about two hours for samples stored at ambient conditions and within several seconds for samples immersed in water. The volume-distributed doublet decays within a few minutes in water, several hours at ambient conditions and several days in vacuum. The anisotropic signal may also be generated by both ionizing radiation and mechanical stress; this signal is quite stable in vacuum and decays over several days at ambient conditions or a few tens of minutes in water. The reference lines for the above-described three EPR signals were obtained and a procedure of spectra deconvolution was developed and tested on samples exposed to both ionizing radiation and mechanical stress.

Nanoscale Environment Sensing Scheme with Brownian Nanorod and Plasmon Resonator

Tracking a Brownian particle’s motion allows localized parameters at its immediate vicinity to be measured. In this, the introduction of a rod that is drawn by a tunable attractive force to a cylindrical pillar overcomes the problems of the particle drifting away from the venue of measurement as well as colliding with other particles. With nanoscale particles, fluorescence labeling suffers from photobleaching and erratic signal due to blinking, while monitoring the polarization of scattered light is limited by the accuracy of correlating the rotational state of the rod to intensity changes. Here, we advance having the cylindrical pillar operate as a surface plasmon-based optical resonator to sense the contacts of nanorods. Simulations with a one-dimensional summed difference expression developed to reduce the difficulty of analyzing a three-dimensional dataset comprising wavelength, rod orientation, and gap distance allowed us to confirm distinct changes in transmission at 600 nm across all orientation angles with contact to noncontact or vice versa. This allows application of a cutoff transmission threshold. The metric f, which defines the proportion of incidences when the nanorod moves freely under Brownian motion influence, showed reduction with normalized charge increase. Good linear sensitivity responses were found at specific ranges in the f versus normalized charge relationship, which when correlated with temperature T, showed df/dT to be maximal when the normalized charge product value was −200. From an uncertainty estimation conducted, a restriction to 1 standard deviation variation necessitated only O(10−2) seconds of sampling using standard photodetectors. This portends significant advantages when sensing environments that are changing temporally rapidly.

Effect of Sampling Frequency on Perfusion Values in Perfusion CT of Lung Tumors

The purpose of this study was to assess as a potential means of limiting radiation exposure the effect on perfusion CT values of increasing sampling intervals in lung perfusion CT acquisition. Lung perfusion CT datasets in patients with lung tumors (> 2.5 cm diameter) were analyzed by distributed parameter modeling to yield tumor blood flow, blood volume, mean transit time, and permeability values. Scans were obtained 2-7 days apart with a 16-MDCT scanner without intervening therapy. Linear mixed-model analyses were used to compare perfusion CT values for the reference standard sampling interval of 0.5 second with those of datasets obtained at sampling intervals of 1, 2, and 3 seconds, which included relative shifts to account for uncertainty in preenhancement set points. Scan-rescan reproducibility was assessed by between-visit coefficient of variation. Twenty-four lung perfusion CT datasets in 12 patients were analyzed. With increasing sampling interval, mean and 95% CI blood flow and blood volume values were increasingly overestimated by up to 14% (95% CI, 11-18%) and 8% (95% CI, 5-11%) at the 3-second sampling interval, and mean transit time and permeability values were underestimated by up to 11% (95% CI, 9-13%) and 3% (95% CI, 1-6%) compared with the results in the standard sampling interval of 0.5 second. The differences were significant for blood flow, blood volume, and mean transit time for sampling intervals of 2 and 3 seconds (p ≤ 0.0002) but not for the 1-second sampling interval. The between-visit coefficient of variation increased with subsampling for blood flow (32.9-34.2%), blood volume (27.1-33.5%), and permeability (39.0-42.4%) compared with the values in the 0.5-second sampling interval (21.3%, 23.6%, and 32.2%). Increasing sampling intervals beyond 1 second yields significantly different perfusion CT parameter values compared with the reference standard (up to 18% for 3 seconds of sampling). Scan-rescan reproducibility is also adversely affected.

Evaluating a direct swabbing method for screening pesticides on fruit and vegetable surfaces using direct analysis in real time (DART) coupled to an Exactive benchtop orbitrap mass spectrometer

Rapid screening of pesticides present on the surfaces of fruits and vegetables has been facilitated by using a Direct Analysis in Real Time (DART(®)) open air surface desorption ionization source coupled to an Exactive(®) high-resolution accurate mass benchtop orbitrap mass spectrometer. The use of cotton and polyester cleaning swabs to collect and retain pesticides for subsequent open air desorption ionization is demonstrated by sampling the surface of various produce to which solutions of pesticides have been applied at levels 10 and 100 times below the tolerance levels established by the United States Environmental Protection Agency (US EPA). Samples analyzed include cherry tomatoes, oranges, peaches and carrots each chosen for their surface characteristics which include: smooth, pitted, fuzzy, and rough respectively. Results from the direct analysis of fungicides on store-bought oranges are also described. In all cases, the swabs were introduced directly into the heated ionizing gas of the DART source resulting in production of protonated pesticide molecules within seconds of sampling. Operation of the orbitrap mass spectrometer at 25,000 full-width half maximum resolution was sufficient to generate high-quality accurate mass data. Stable external mass calibration eliminated the need for addition of standards typically required for mass calibration, thus allowing multiple analyses to be completed without instrument recalibration.

Evaluation of Detection Performance of Portable Aspiration-Type Ion Mobility Spectrometer with Seven Detection Cells for Chemical Warfare Agents

The detection performance of a portable 241Am ionization aspiration-type ion mobility spectrometer (M90-D1-C, Environics Oy) was investigated with nerve gases, blister agents, blood agents, choking agents and related compounds. The vapors of nerve gases, sarin, soman, tabun, cyclohexylsarin were recognized as "NERVE" after about several seconds of sampling, and the limits of detection (LOD) were < 0.3 mg m−3. The vapors of blister agents, mustard gas and lewisite 1, and blood agents, hydrogen cyanide and cyanogen chloride were recognized as "BLISTER" with an LOD of < 2.4 mg m−3 and > 415 mg m−3, respectively. The vapor of chlorine was recognized as "BLOOD" with an LOD of 820 mg m−3. The vapors of nitrogen mustard 3 and chlorpicrin were recognized as different alarm classes, depending on their concentrations. The vapors of nitrogen mustard 1, 2 and phosgene did not show any alarm. As for interference, the vapors of nerve gas simulants, dimethylmethylphosphonate, trimethylphosphate, triethylphosphate, diisopropylfluorophosphate, blister agent simulants, 2-chloroethylethylsulfide, 1,4-thioxane, 2-mercaptoethanol, and 20 organic solvents within 38 solvents examined were recognized false-positively. The patterns of detection sensor channel response values of 6 ion mobility cells and semiconductor cell were compared with the situation of the alarm against chemical-warfare agents.

Detection Performance of Portable Colona Discharge Ionization Type Ion Mobility Spectrometer for Chemical Warfare Agents

The detection performance of a portable corona discharge ionization-type ion mobility spectrometer (LCD 3.2E, Smiths Detection) was investigated using nerve gases, blister agents, blood agents and related compounds. The vapors of sarin, soman and tabun were recognized as "G" after about several seconds of sampling; the detection limits were around 0.2 mg/m3. The vapors of mustard gas, lewisite 1, hydrogen cyanide and chloropicrin were recognized as "H" after several seconds of sampling, and the detection limits were around 10 mg/m3. The vapors of cyanogen chloride were also recognized as "H", but the detection limit was around 500 mg/m3. The vapors of trimethylphosphate, triethylphosphate, n-propanol, diethylamine, triethylamine, formaldehyde, and N,N-dimethylformamide were recognized as "G", and the vapors of 1,4-thioxane, 2-mercaptoethanol, diethylether and acetic acid were recognized as "H".

Fast filter-sampling and analysis of PAH aerosols by laser multiphoton ionization

Most current methods for analysis of airborne polycyclic aromatic hydrocarbon (PAH) aerosols are based on filter sampling. We propose a new method for fast screening of the PAH contaminated filters, using laser induced multiphoton ionization (MPI), coupled to a fast-conductance (FC) detection scheme. We show that the porous morphology of glass fiber filters allows direct application of the MPI-FC technique. The results obtained by this method are compared to traditional solvent extraction followed by liquid chromatographic analysis. It has been found that the MPI-FC data represent a surface analysis, rather than a bulk integration. This has been confirmed by performing fluorescence imaging microscopy on the same filters. The calibration plots of the MPI-FC method are linear as long as the outer surface of the sampling filter is not saturated with PAH particulates. When stacking of particulates starts, quantification fails. Several other limitations, resulting from the very nature of this method, are discussed. The sensitivity for PAHs is adequate for environmental analysis and MPI readouts can be obtained after only a few seconds of sampling. Therefore, it is concluded that the method can probably be used for fast screening of PAH aerosols, and for providing the first indication of such a contamination.

Surface electrical capacitance as an index of epidermal barrier properties of composite skin substitutes and skin autografts

Restoration of the epidermal barrier is a requirement for burn wound closure. A rapid, reliable, and noninvasive measure of the rate of restoration of the epidermal barrier is not readily available. To monitor the reformation of the epidermal barrier, we measured surface electrical capacitance on cultured skin substitutes (human keratinocytes and fibroblasts attached to collagen-glycosaminoglycan substrates) and split-thickness skin autografts grafted to patients. Data were collected from four patients with burns and one pediatric patient with a congenital hairy nevus comprising > 60% total body surface area. Capacitance measurements were performed at days 7, 10, 12, 14, and 28 by direct contact of the capacitance probe for 10 seconds to the cultured skin substitutes or split-thickness autograft. On postoperative days 7, 10, 12, 14, 21, and 28, the surface electrical capacitance of cultured skin substitutes after 10 seconds of sampling was 2468 +/- 268, 1443 +/- 439, 129 +/- 43, 200 +/- 44, 88 +/- 20, and 74 +/- 19 picofarads (mean +/- standard error of the mean), respectively. Surface electrical capacitance for split-thickness autograft on the same days was 1699 +/- 371, 1914 +/- 433, 125 +/- 16, 175 +/- 63, 110 +/- 26, 271 +/- 77 picofarads, respectively. Surface electrical capacitance in all of the grafts decreased with time. Cultured skin substitutes had approximately the same 10-second capacitance values as split-thickness autograft during 3 weeks of healing and approached values for uninjured skin (32 +/- 5 picofarads) by 12 days. Measurement of surface electrical capacitance is a direct, inexpensive, and convenient index for noninvasive monitoring of epidermal barrier formation.