Digital enzyme-linked immunosorbent assays with sub-attomolar detection limits based on low numbers of capture beads combined with high efficiency bead analysis

Lab on a Chip ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 2122-2135
Author(s):  
Cheuk W. Kan ◽  
Carmen I. Tobos ◽  
David M. Rissin ◽  
Alexander D. Wiener ◽  
Ray E. Meyer ◽  
...  
Keyword(s):  
High Efficiency ◽  
Detection Limits ◽  
Immunosorbent Assays ◽  
Digital Elisa

We report approaches to improve the sensitivity of digital ELISA up to 400-fold, enabling detection of proteins at subattomolar concentrations.

scholarly journals Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in Stool

2015 ◽  
Vol 53 (10) ◽  
pp. 3204-3212 ◽  
Author(s):  
Linan Song ◽  
Mingwei Zhao ◽  
David C. Duffy ◽  
Joshua Hansen ◽  
Kelsey Shields ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Cytotoxicity Assay ◽  
Nucleic Acid Amplification ◽  
Analytical Sensitivity ◽  
Toxin B ◽  
Content Type ◽  
Toxigenic Culture ◽  
Immunosorbent Assays ◽  
Digital Elisa ◽  
Detection And Quantification

The currently available diagnostics forClostridium difficileinfection (CDI) have major limitations. Despite mounting evidence that toxin detection is paramount for diagnosis, conventional toxin immunoassays are insufficiently sensitive and cytotoxicity assays too complex; assays that detect toxigenic organisms (toxigenic culture [TC] and nucleic acid amplification testing [NAAT]) are confounded by asymptomatic colonization by toxigenicC. difficile. We developed ultrasensitive digital enzyme-linked immunosorbent assays (ELISAs) for toxins A and B using single-molecule array technology and validated the assays using (i) culture filtrates from a panel of clinicalC. difficileisolates and (ii) 149 adult stool specimens already tested routinely by NAAT. The digital ELISAs detected toxins A and B in stool with limits of detection of 0.45 and 1.5 pg/ml, respectively, quantified toxins across a 4-log range, and detected toxins from all clinical strains studied. Using specimens that were negative by cytotoxicity assay/TC/NAAT, clinical cutoffs were set at 29.4 pg/ml (toxin A) and 23.3 pg/ml (toxin B); the resulting clinical specificities were 96% and 98%, respectively. The toxin B digital ELISA was 100% sensitive versus cytotoxicity assay. Twenty-five percent and 22% of the samples positive by NAAT and TC, respectively, were negative by the toxin B digital ELISA, consistent with the presence of organism but minimal or no toxin. The mean toxin levels by digital ELISA were 1.5- to 1.7-fold higher in five patients with CDI-attributable severe outcomes, versus 68 patients without, but this difference was not statistically significant. Ultrasensitive digital ELISAs for the detection and quantification of toxins A and B in stool can provide a rapid and simple tool for the diagnosis of CDI with both high analytical sensitivity and high clinical specificity.

scholarly journals Determination of the content of impurity elements in a sample of high purity India by the method of radiochemical neutron activation analysis

2022 ◽  
Vol 2155 (1) ◽  
pp. 012023
Author(s):  
I.I. Sadikov ◽  
B. Kh. Yarmatov ◽  
T.M. Usmanov ◽  
Z.O. Sadikova
Keyword(s):  
Neutron Activation Analysis ◽  
Activation Analysis ◽  
Neutron Activation ◽  
High Purity ◽  
High Efficiency ◽  
Detection Limits ◽  
Radiochemical Neutron Activation Analysis ◽  
Pure Substances ◽  
Impurity Elements

Abstract The present article is devoted to the development of a method for neutron activation analysis of a microimpurity composition of high-purity indium with the radiochemical separation of indium radionuclides from radionuclides of the determined elements by extraction chromatography in the system tributyl phosphate (TBP) - solutions of hydrobromic acid (HBr). Neutron activation analysis (NAA) has a special place among the physical methods for determining the trace composition of high-purity substances. Low detection limits, the possibility of simultaneous determination of a large number of impurity elements from one sample, no correction for the control experiment, the possibility of using inactive carriers in separating traces of radionuclides of impurity elements from matrix elements ensured the widespread use of NAA in the analysis of highly pure substances. The developed technique allows separating matrix radionuclides from radionuclides of impurity elements with high efficiency and determination of 28 impurity elements in high-purity indium with detection limits of 0.7 ppm to 0.05 ppb.

Characterization of a High-Efficiency Helium Microwave-Induced Plasma as an Atomization Source for Atomic Spectrometric Analysis

1989 ◽  
Vol 43 (3) ◽  
pp. 499-504 ◽  
Author(s):  
Larry D. Perkins ◽  
Gary L. Long
Keyword(s):  
High Efficiency ◽  
Detection Limits ◽  
Atomic Emission ◽  
Fluorescence Spectrometry ◽  
Emission Spectrometry ◽  
Spectrometric Analysis ◽  
Atomic Fluorescence Spectrometry ◽  
Atomic Fluorescence ◽  
Microwave Induced Plasma

Characterization studies of a He high-efficiency microwave-induced plasma, He-HEMIP, utilizing direct sample introduction with pneumatic nebulization for atomic emission and atomic fluorescence spectrometry are presented. These studies include diagnostic measurements and analytical characterization of the 150-W He-HEMIP. Diagnostic measurements include excitation temperatures with the use of aqueous and organic nebulized thermometric species, electron number densities, and ionization temperatures for the plasma. The effect of sample uptake rate on the emission intensity is investigated. Ionization interferences are minimal, and phosphate interferences were found not to occur. In addition, the He-HEMIP is characterized as an atom source for metals and nonmetals with the use of atomic emission spectrometry and atomic fluorescence spectrometry. With AES, detection limits for metals and nonmetals are in the sub-ppm range. With AFS, detection limits for metals were determined to be in the low to sub-ppb range and were found to be not statistically different from those reported for HCL-ICP-AFS. Linear ranges for AES and AFS ranged from four up to five and one-half orders of concentrative magnitude.

Microcalorimeters for X-Ray Spectroscopy

1988 ◽  
Vol 102 ◽  
pp. 41
Author(s):  
E. Silver ◽  
C. Hailey ◽  
S. Labov ◽  
N. Madden ◽  
D. Landis ◽  
...  
Keyword(s):  
High Resolution ◽  
High Efficiency ◽  
Thermal Response ◽  
Low Noise ◽  
High Resolution Spectroscopy ◽  
Superconducting Transition ◽  
Sapphire Substrates ◽  
Laboratory Plasmas ◽  
Adiabatic Demagnetization ◽  
Theoretical Predictions

The merits of microcalorimetry below 1°K for high resolution spectroscopy has become widely recognized on theoretical grounds. By combining the high efficiency, broadband spectral sensitivity of traditional photoelectric detectors with the high resolution capabilities characteristic of dispersive spectrometers, the microcalorimeter could potentially revolutionize spectroscopic measurements of astrophysical and laboratory plasmas. In actuality, however, the performance of prototype instruments has fallen short of theoretical predictions and practical detectors are still unavailable for use as laboratory and space-based instruments. These issues are currently being addressed by the new collaborative initiative between LLNL, LBL, U.C.I., U.C.B., and U.C.D.. Microcalorimeters of various types are being developed and tested at temperatures of 1.4, 0.3, and 0.1°K. These include monolithic devices made from NTD Germanium and composite configurations using sapphire substrates with temperature sensors fabricated from NTD Germanium, evaporative films of Germanium-Gold alloy, or material with superconducting transition edges. A new approache to low noise pulse counting electronics has been developed that allows the ultimate speed of the device to be determined solely by the detector thermal response and geometry. Our laboratory studies of the thermal and resistive properties of these and other candidate materials should enable us to characterize the pulse shape and subsequently predict the ultimate performance. We are building a compact adiabatic demagnetization refrigerator for conveniently reaching 0.1°K in the laboratory and for use in future satellite-borne missions. A description of this instrument together with results from our most recent experiments will be presented.

Imaging and diffraction modes in Scanning Transmission Electron Microscopy

1986 ◽  
Vol 44 ◽  
pp. 684-687
Author(s):  
J. M. Cowley ◽  
R. Glaisher ◽  
J. A. Lin ◽  
H.-J. Ou
Keyword(s):  
Scanning Transmission Electron Microscopy ◽  
High Efficiency ◽  
Fiber Optic ◽  
Image Intensifier ◽  
Detector System ◽  
Detector Plane ◽  
Secondary Electrons ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Special Detector

Some of the most important applications of STEM depend on the variety of imaging and diffraction made possible by the versatility of the detector system and the serial nature, of the image acquisition. A special detector system, previously described, has been added to our STEM instrument to allow us to take full advantage of this versatility. In this, the diffraction pattern in the detector plane may be formed on either of two phosphor screens, one with P47 (very fast) phosphor and the other with P20 (high efficiency) phosphor. The light from the phosphor is conveyed through a fiber-optic rod to an image intensifier and TV system and may be photographed, recorded on videotape, or stored digitally on a frame store. The P47 screen has a hole through it to allow electrons to enter a Gatan EELS spectrometer. Recently a modified SEM detector has been added so that high resolution (10Å) imaging with secondary electrons may be used in conjunction with other modes.

Quantitative parallel EELS spectrum imaging developed as a new tool in AEM

1992 ◽  
Vol 50 (2) ◽  
pp. 1202-1203
Author(s):  
Gianluigi Botton ◽  
Gilles L'espérance
Keyword(s):  
Statistical Analysis ◽  
Spatial Resolution ◽  
Personal Computer ◽  
Systematic Study ◽  
Present Author ◽  
Chemical Elements ◽  
Detection Limits ◽  
Research Groups ◽  
Quantitative Performance ◽  
Spectrum Imaging

As interest for parallel EELS spectrum imaging grows in laboratories equipped with commercial spectrometers, different approaches were used in recent years by a few research groups in the development of the technique of spectrum imaging as reported in the literature. Either by controlling, with a personal computer both the microsope and the spectrometer or using more powerful workstations interfaced to conventional multichannel analysers with commercially available programs to control the microscope and the spectrometer, spectrum images can now be obtained. Work on the limits of the technique, in terms of the quantitative performance was reported, however, by the present author where a systematic study of artifacts detection limits, statistical errors as a function of desired spatial resolution and range of chemical elements to be studied in a map was carried out The aim of the present paper is to show an application of quantitative parallel EELS spectrum imaging where statistical analysis is performed at each pixel and interpretation is carried out using criteria established from the statistical analysis and variations in composition are analyzed with the help of information retreived from t/γ maps so that artifacts are avoided.

Influence of MBE Growth Conditions on Dislocation Densities of GaAs/Ge Epilayers Grown on Silicon Substrates

1985 ◽  
Vol 43 ◽  
pp. 364-365
Author(s):  
K.M. Hones ◽  
P. Sheldon ◽  
B.G. Yacobi ◽  
A. Mason
Keyword(s):  
High Efficiency ◽  
Lattice Mismatch ◽  
Low Cost ◽  
Growth Conditions ◽  
Nonradiative Recombination ◽  
Device Structure ◽  
Si Substrates ◽  
Transmission Electron ◽  
Dislocation Densities ◽  
Dislocation Type

There is increasing interest in growing epitaxial GaAs on Si substrates. Such a device structure would allow low-cost substrates to be used for high-efficiency cascade- junction solar cells. However, high-defect densities may result from the large lattice mismatch (∼4%) between the GaAs epilayer and the silicon substrate. These defects can act as nonradiative recombination centers that can degrade the optical and electrical properties of the epitaxially grown GaAs. For this reason, it is important to optimize epilayer growth conditions in order to minimize resulting dislocation densities. The purpose of this paper is to provide an indication of the quality of the epitaxially grown GaAs layers by using transmission electron microscopy (TEM) to examine dislocation type and density as a function of various growth conditions. In this study an intermediate Ge layer was used to avoid nucleation difficulties observed for GaAs growth directly on Si substrates. GaAs/Ge epilayers were grown by molecular beam epitaxy (MBE) on Si substrates in a manner similar to that described previously.

The use of high-resolution FESEM to study solid-state phase transformations and reactions

1994 ◽  
Vol 52 ◽  
pp. 1028-1029
Author(s):  
P. G. Kotula ◽  
D. D. Erickson ◽  
C. B. Carter
Keyword(s):  
Solid State ◽  
High Resolution ◽  
Phase Transformations ◽  
High Efficiency ◽  
Sol Gel ◽  
Quantitative Information ◽  
Solid State Reactions ◽  
Critical Dimensions ◽  
Backscattered Electrons ◽  
Backscattered Electron

High-resolution field-emission-gun scanning electron microscopy (FESEM) has recently emerged as an extremely powerful method for characterizing the micro- or nanostructure of materials. The development of high efficiency backscattered-electron detectors has increased the resolution attainable with backscattered-electrons to almost that attainable with secondary-electrons. This increased resolution allows backscattered-electron imaging to be utilized to study materials once possible only by TEM. In addition to providing quantitative information, such as critical dimensions, SEM is more statistically representative. That is, the amount of material that can be sampled with SEM for a given measurement is many orders of magnitude greater than that with TEM.In the present work, a Hitachi S-900 FESEM (operating at 5kV) equipped with a high-resolution backscattered electron detector, has been used to study the α-Fe2O3 enhanced or seeded solid-state phase transformations of sol-gel alumina and solid-state reactions in the NiO/α-Al2O3 system. In both cases, a thin-film cross-section approach has been developed to facilitate the investigation. Specifically, the FESEM allows transformed- or reaction-layer thicknesses along interfaces that are millimeters in length to be measured with a resolution of better than 10nm.

Analysis of completed commercial semiconductors using EPMA

1996 ◽  
Vol 54 ◽  
pp. 502-503
Author(s):  
R. Packwood ◽  
M.W. Phaneuf ◽  
V. Weatherall ◽  
I. Bassignana
Keyword(s):  
Electron Probe Microanalysis ◽  
Electron Probe ◽  
Semiconductor Industry ◽  
Detection Limits ◽  
High Technology ◽  
Depth Resolution ◽  
Analytical Instruments ◽  
Wide Range ◽  
Numerous Element ◽  
Choice Method

The development of specialized analytical instruments such as the SIMS, XPS, ISS etc., all with truly incredible abilities in certain areas, has given rise to the notion that electron probe microanalysis (EPMA) is an old fashioned and rather inadequate technique, and one that is of little or no use in such high technology fields as the semiconductor industry. Whilst it is true that the microprobe does not possess parts-per-billion sensitivity (ppb) or monolayer depth resolution it is also true that many times these extremes of performance are not essential and that a few tens of parts-per-million (ppm) and a few tens of nanometers depth resolution is all that is required. In fact, the microprobe may well be the second choice method for a wide range of analytical problems and even the method of choice for a few.The literature is replete with remarks that suggest the writer is confusing an SEM-EDXS combination with an instrument such as the Cameca SX-50. Even where this confusion does not exist, the literature discusses microprobe detection limits that are seldom stated to be as low as 100 ppm, whereas there are numerous element combinations for which 10-20 ppm is routinely attainable.

Interlayer confinement synthesis of Ir nanodots/dual carbon as an electrocatalyst for overall water splitting

2020 ◽  
Author(s):  
Yaru Li ◽  
Yu-Quan Zhu ◽  
Weili Xin ◽  
Song Hong ◽  
Xiaoying Zhao ◽  
...  
Keyword(s):  
Water Splitting ◽  
Noble Metal ◽  
High Efficiency ◽  
Overall Water Splitting ◽  
Highly Dispersed

Rationally designing low-content and high-efficiency noble metal nanodots offers opportunities to enhance electrocatalytic performances for water splitting. However, the preparation of highly dispersed nanodots electrocatalysts remains a challenge. Herein, we...

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