High-sensitivity chemical imaging for biomedicine by SRS microscopy (Conference Presentation)

Author(s):  
Wei Min
2021 ◽  
Vol 6 (1) ◽  
pp. 73
Author(s):  
Kenta Iitani ◽  
Koji Toma ◽  
Takahiro Arakawa ◽  
Kohji Mitsubayashi

Many gas-phase biosensors have been developed for human volatiles (acetone, methyl mercaptan, trimethylamine, ethanol, isopropanol, etc.) and for residential harmful VOCs (formaldehyde, toluene, nicotine) causing some diseases. A novel gas-imaging system by biofluorometry with an enzyme immobilized mesh was investigated to demonstrate spatiotemporal gas-imaging for human volatiles (i.e., ethanol and acetaldehyde after drinking). A biofluorometric technique was applied to improve the performance (sensitivity, calibration range, gas-selectivity, etc.) of the gas-imaging system. The biofluorometric sniff-cam for ethanol was fabricated with an ADH (alcohol dehydrogenase) immobilized mesh and an NADH fluorescent visualization unit (UV-LED sheet array and highly sensitive camera); thus, showing the two-dimensional real-time imaging of ethanol vapor distribution (0.5–200 ppm). The system showed rapid and accurate responses and a visible measurement of ethanol in the gas phase. The intensity of fluorescence was linearly related to the concentration of ethanol vapor. The high sensitivity fluorescent imaging of ethanol vapor allows to successfully visualize gaseous ethanol from the human body (exhaled air and skin gas) after drinking. The sniff-cam system would be useful for the conventional detecting and imaging of the volatile biomarkers.


2016 ◽  
Vol 187 ◽  
pp. 135-154 ◽  
Author(s):  
Michael J. Pilling ◽  
Alex Henderson ◽  
Benjamin Bird ◽  
Mick D. Brown ◽  
Noel W. Clarke ◽  
...  

Infrared microscopy has become one of the key techniques in the biomedical research field for interrogating tissue. In partnership with multivariate analysis and machine learning techniques, it has become widely accepted as a method that can distinguish between normal and cancerous tissue with both high sensitivity and high specificity. While spectral histopathology (SHP) is highly promising for improved clinical diagnosis, several practical barriers currently exist, which need to be addressed before successful implementation in the clinic. Sample throughput and speed of acquisition are key barriers and have been driven by the high volume of samples awaiting histopathological examination. FTIR chemical imaging utilising FPA technology is currently state-of-the-art for infrared chemical imaging, and recent advances in its technology have dramatically reduced acquisition times. Despite this, infrared microscopy measurements on a tissue microarray (TMA), often encompassing several million spectra, takes several hours to acquire. The problem lies with the vast quantities of data that FTIR collects; each pixel in a chemical image is derived from a full infrared spectrum, itself composed of thousands of individual data points. Furthermore, data management is quickly becoming a barrier to clinical translation and poses the question of how to store these incessantly growing data sets. Recently, doubts have been raised as to whether the full spectral range is actually required for accurate disease diagnosis using SHP. These studies suggest that once spectral biomarkers have been predetermined it may be possible to diagnose disease based on a limited number of discrete spectral features. In this current study, we explore the possibility of utilising discrete frequency chemical imaging for acquiring high-throughput, high-resolution chemical images. Utilising a quantum cascade laser imaging microscope with discrete frequency collection at key diagnostic wavelengths, we demonstrate that we can diagnose prostate cancer with high sensitivity and specificity. Finally we extend the study to a large patient dataset utilising tissue microarrays, and show that high sensitivity and specificity can be achieved using high-throughput, rapid data collection, thereby paving the way for practical implementation in the clinic.


Author(s):  
S. H. Lau ◽  
Benjamin Stripe ◽  
Sylvia Lewis ◽  
Xiaolin Yang ◽  
Wenbing Yun

Abstract New heterogeneous 3D integration schemes and continuing miniaturization of semiconductor packaging components, such as micropillars, are driving demand for substantive changes to conventional PFA (physical failure analysis). In particular, desired performance capabilities include the ability to nondestructively determine failures within seconds to minutes. New tools should be quantitative, have sufficient resolution to determine sub-micron sized defects and voids in TSVs at the wafer or package level. It should also measure thickness and their material composition of multilayer structures above the wafer surface, such as microbumps, or those below the surface including UBM and RDL. In this paper we are introducing a novel x-ray fluorescence microscope technique capable of solving the above applications in advanced packaging for PFA and process development. The same technique can also be applied in the front end metrology of new gate materials, 3D FinFET structures within test structures in patterned wafers. Characterization of sub nanoscopic changes (sensitivity of sub-angstrom) in film and dopants deposited in 3D structures will also be shown. With its high sensitivity for trace materials, contamination analysis of post hard mask residue, post metal etch residue especially in high aspect ratio structures is also possible.


2020 ◽  
Vol 6 (37) ◽  
pp. eabb3615 ◽  
Author(s):  
A. Pattammattel ◽  
R. Tappero ◽  
M. Ge ◽  
Y. S. Chu ◽  
X. Huang ◽  
...  

Resolving chemical species at the nanoscale is of paramount importance to many scientific and technological developments across a broad spectrum of disciplines. Hard x-rays with excellent penetration power and high chemical sensitivity are suitable for speciation of heterogeneous (thick) materials. Here, we report nanoscale chemical speciation by combining scanning nanoprobe and fluorescence-yield x-ray absorption near-edge structure (nano-XANES). First, the resolving power of nano-XANES was demonstrated by mapping Fe(0) and Fe(III) states of a reference sample composed of stainless steel and hematite nanoparticles with 50-nm scanning steps. Nano-XANES was then used to study the trace secondary phases in lithium iron phosphate (LFP) particles. We observed individual Fe-phosphide nanoparticles in pristine LFP, whereas partially (de)lithiated particles showed Fe-phosphide nanonetworks. These findings shed light on the contradictory reports on Fe-phosphide morphology in the literature. Nano-XANES bridges the capability gap of spectromicroscopy methods and provides exciting research opportunities across multiple disciplines.


1994 ◽  
Vol 144 ◽  
pp. 21-28 ◽  
Author(s):  
G. B. Gelfreikh

AbstractA review of methods of measuring magnetic fields in the solar corona using spectral-polarization observations at microwaves with high spatial resolution is presented. The methods are based on the theory of thermal bremsstrahlung, thermal cyclotron emission, propagation of radio waves in quasi-transverse magnetic field and Faraday rotation of the plane of polarization. The most explicit program of measurements of magnetic fields in the atmosphere of solar active regions has been carried out using radio observations performed on the large reflector radio telescope of the Russian Academy of Sciences — RATAN-600. This proved possible due to good wavelength coverage, multichannel spectrographs observations and high sensitivity to polarization of the instrument. Besides direct measurements of the strength of the magnetic fields in some cases the peculiar parameters of radio sources, such as very steep spectra and high brightness temperatures provide some information on a very complicated local structure of the coronal magnetic field. Of special interest are the results found from combined RATAN-600 and large antennas of aperture synthesis (VLA and WSRT), the latter giving more detailed information on twodimensional structure of radio sources. The bulk of the data obtained allows us to investigate themagnetospheresof the solar active regions as the space in the solar corona where the structures and physical processes are controlled both by the photospheric/underphotospheric currents and surrounding “quiet” corona.


Author(s):  
Kazumichi Ogura ◽  
Michael M. Kersker

Backscattered electron (BE) images of GaAs/AlGaAs super lattice structures were observed with an ultra high resolution (UHR) SEM JSM-890 with an ultra high sensitivity BE detector. Three different types of super lattice structures of GaAs/AlGaAs were examined. Each GaAs/AlGaAs wafer was cleaved by a razor after it was heated for approximately 1 minute and its crosssectional plane was observed.First, a multi-layer structure of GaAs (100nm)/AlGaAs (lOOnm) where A1 content was successively changed from 0.4 to 0.03 was observed. Figures 1 (a) and (b) are BE images taken at an accelerating voltage of 15kV with an electron beam current of 20pA. Figure 1 (c) is a sketch of this multi-layer structure corresponding to the BE images. The various layers are clearly observed. The differences in A1 content between A1 0.35 Ga 0.65 As, A1 0.4 Ga 0.6 As, and A1 0.31 Ga 0.69 As were clearly observed in the contrast of the BE image.


Author(s):  
D. A. Carpenter ◽  
M. A. Taylor

The development of intense sources of x rays has led to renewed interest in the use of microbeams of x rays in x-ray fluorescence analysis. Sparks pointed out that the use of x rays as a probe offered the advantages of high sensitivity, low detection limits, low beam damage, and large penetration depths with minimal specimen preparation or perturbation. In addition, the option of air operation provided special advantages for examination of hydrated systems or for nondestructive microanalysis of large specimens.The disadvantages of synchrotron sources prompted the development of laboratory-based instrumentation with various schemes to maximize the beam flux while maintaining small point-to-point resolution. Nichols and Ryon developed a microprobe using a rotating anode source and a modified microdiffractometer. Cross and Wherry showed that by close-coupling the x-ray source, specimen, and detector, good intensities could be obtained for beam sizes between 30 and 100μm. More importantly, both groups combined specimen scanning with modern imaging techniques for rapid element mapping.


Author(s):  
T. M. Weatherby ◽  
P.H. Lenz

Crustaceans, as well as other arthropods, are covered with sensory setae and hairs, including mechanoand chemosensory sensillae with a ciliary origin. Calanoid copepods are small planktonic crustaceans forming a major link in marine food webs. In conjunction with behavioral and physiological studies of the antennae of calanoids, we undertook the ultrastructural characterization of sensory setae on the antennae of Pleuromamma xiphias.Distal mechanoreceptive setae exhibit exceptional behavioral and physiological performance characteristics: high sensitivity (<10 nm displacements), fast reaction times (<1 msec latency) and phase locking to high frequencies (1-2 kHz). Unusual structural features of the mechanoreceptors are likely to be related to their physiological sensitivity. These features include a large number (up to 3000) of microtubules in each sensory cell dendrite, arising from or anchored to electron dense rods associated with the ciliary basal body microtubule doublets. The microtubules are arranged in a regular array, with bridges between and within rows. These bundles of microtubules extend far into each mechanoreceptive seta and terminate in a staggered fashion along the dendritic membrane, contacting a large membrane surface area and providing a large potential site of mechanotransduction.


Author(s):  
F. Ouyang ◽  
D. A. Ray ◽  
O. L. Krivanek

Electron backscattering Kikuchi diffraction patterns (BKDP) reveal useful information about the structure and orientation of crystals under study. With the well focused electron beam in a scanning electron microscope (SEM), one can use BKDP as a microanalysis tool. BKDPs have been recorded in SEMs using a phosphor screen coupled to an intensified TV camera through a lens system, and by photographic negatives. With the development of fiber-optically coupled slow scan CCD (SSC) cameras for electron beam imaging, one can take advantage of their high sensitivity and wide dynamic range for observing BKDP in SEM.We have used the Gatan 690 SSC camera to observe backscattering patterns in a JEOL JSM-840A SEM. The CCD sensor has an active area of 13.25 mm × 8.83 mm and 576 × 384 pixels. The camera head, which consists of a single crystal YAG scintillator fiber optically coupled to the CCD chip, is located inside the SEM specimen chamber. The whole camera head is cooled to about -30°C by a Peltier cooler, which permits long integration times (up to 100 seconds).


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