An electron microscope is a microscope that uses a beam of electrons as a source of illumination. They use electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing them to produce magnified images or electron diffraction patterns. As the wavelength of an electron can be up to 100,000 times smaller than that of visible light, electron microscopes have a much higher resolution of about 0.1 nm, which compares to about 200 nm for light microscopes. Electron microscope may refer to:
Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye. There are three well-known branches of microscopy: optical, electron, and scanning probe microscopy, along with the emerging field of X-ray microscopy.
The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microscope and were possibly invented in their present compound form in the 17th century. Basic optical microscopes can be very simple, although many complex designs aim to improve resolution and sample contrast.
Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the optical diffraction limit.
Confocal microscopy, most frequently confocal laser scanning microscopy (CLSM) or laser scanning confocal microscopy (LSCM), is an optical imaging technique for increasing optical resolution and contrast of a micrograph by means of using a spatial pinhole to block out-of-focus light in image formation. Capturing multiple two-dimensional images at different depths in a sample enables the reconstruction of three-dimensional structures within an object. This technique is used extensively in the scientific and industrial communities and typical applications are in life sciences, semiconductor inspection and materials science.
BrainMaps is an NIH-funded interactive zoomable high-resolution digital brain atlas and virtual microscope that is based on more than 140 million megapixels of scanned images of serial sections of both primate and non-primate brains and that is integrated with a high-speed database for querying and retrieving data about brain structure and function over the internet.
High-content screening (HCS), also known as high-content analysis (HCA) or cellomics, is a method that is used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell in a desired manner. Hence high content screening is a type of phenotypic screen conducted in cells involving the analysis of whole cells or components of cells with simultaneous readout of several parameters. HCS is related to high-throughput screening (HTS), in which thousands of compounds are tested in parallel for their activity in one or more biological assays, but involves assays of more complex cellular phenotypes as outputs. Phenotypic changes may include increases or decreases in the production of cellular products such as proteins and/or changes in the morphology of the cell. Hence HCA typically involves automated microscopy and image analysis. Unlike high-content analysis, high-content screening implies a level of throughput which is why the term "screening" differentiates HCS from HCA, which may be high in content but low in throughput.
Feature-oriented scanning (FOS) is a method of precision measurement of surface topography with a scanning probe microscope in which surface features (objects) are used as reference points for microscope probe attachment. With FOS method, by passing from one surface feature to another located nearby, the relative distance between the features and the feature neighborhood topographies are measured. This approach allows to scan an intended area of a surface by parts and then reconstruct the whole image from the obtained fragments. Beside the mentioned, it is acceptable to use another name for the method – object-oriented scanning (OOS).
Neuronavigation is the set of computer-assisted technologies used by neurosurgeons to guide or "navigate" within the confines of the skull or vertebral column during surgery, and used by psychiatrists to accurately target rTMS. The set of hardware for these purposes is referred to as a neuronavigator.
A virtual slide is created when glass slides are digitally scanned in their entirety to provide a high resolution digital image using a digital scanning system for the purpose of medical digital image analysis. Digital slides can be retrieved from a storage system, and viewed on a computer screen, by running image management software on a standard web browser, and assessed in exactly the same way as on a microscope. Digital slides can be used as an alternative to traditional viewing for the purpose of teleconsultation.
Digital pathology is a sub-field of pathology that focuses on data management based on information generated from digitized specimen slides. Through the use of computer-based technology, digital pathology utilizes virtual microscopy. Glass slides are converted into digital slides that can be viewed, managed, shared and analyzed on a computer monitor. With the practice of Whole-Slide Imaging (WSI), which is another name for virtual microscopy, the field of digital pathology is growing and has applications in diagnostic medicine, with the goal of achieving efficient and cheaper diagnoses, prognosis, and prediction of diseases due to the success in machine learning and artificial intelligence in healthcare.
Cytometry is the measurement of number and characteristics of cells. Variables that can be measured by cytometric methods include cell size, cell count, cell morphology, cell cycle phase, DNA content, and the existence or absence of specific proteins on the cell surface or in the cytoplasm. Cytometry is used to characterize and count blood cells in common blood tests such as the complete blood count. In a similar fashion, cytometry is also used in cell biology research and in medical diagnostics to characterize cells in a wide range of applications associated with diseases such as cancer and AIDS.
Telepathology is the practice of pathology at a distance. It uses telecommunications technology to facilitate the transfer of image-rich pathology data between distant locations for the purposes of diagnosis, education, and research. Performance of telepathology requires that a pathologist selects the video images for analysis and the rendering of diagnoses. The use of "television microscopy", the forerunner of telepathology, did not require that a pathologist have physical or virtual "hands-on" involvement in the selection of microscopic fields-of-view for analysis and diagnosis.
Digital holographic microscopy (DHM) is digital holography applied to microscopy. Digital holographic microscopy distinguishes itself from other microscopy methods by not recording the projected image of the object. Instead, the light wave front information originating from the object is digitally recorded as a hologram, from which a computer calculates the object image by using a numerical reconstruction algorithm. The image forming lens in traditional microscopy is thus replaced by a computer algorithm. Other closely related microscopy methods to digital holographic microscopy are interferometric microscopy, optical coherence tomography and diffraction phase microscopy. Common to all methods is the use of a reference wave front to obtain amplitude (intensity) and phase information. The information is recorded on a digital image sensor or by a photodetector from which an image of the object is created (reconstructed) by a computer. In traditional microscopy, which do not use a reference wave front, only intensity information is recorded and essential information about the object is lost.
Endomicroscopy is a technique for obtaining histology-like images from inside the human body in real-time, a process known as ‘optical biopsy’. It generally refers to fluorescence confocal microscopy, although multi-photon microscopy and optical coherence tomography have also been adapted for endoscopic use. Commercially available clinical and pre-clinical endomicroscopes can achieve a resolution on the order of a micrometre, have a field-of-view of several hundred µm, and are compatible with fluorophores which are excitable using 488 nm laser light. The main clinical applications are currently in imaging of the tumour margins of the brain and gastro-intestinal tract, particularly for the diagnosis and characterisation of Barrett’s Esophagus, pancreatic cysts and colorectal lesions. A number of pre-clinical and transnational applications have been developed for endomicroscopy as it enables researchers to perform live animal imaging. Major pre-clinical applications are in gastro-intestinal tract, toumour margin detection, uterine complications, ischaemia, live imaging of cartilage and tendon and organoid imaging.
An imaging cycler microscope (ICM) is a fully automated (epi)fluorescence microscope which overcomes the spectral resolution limit resulting in parameter- and dimension-unlimited fluorescence imaging. The principle and robotic device was described by Walter Schubert in 1997 and has been further developed with his co-workers within the human toponome project. The ICM runs robotically controlled repetitive incubation-imaging-bleaching cycles with dye-conjugated probe libraries recognizing target structures in situ (biomolecules in fixed cells or tissue sections). This results in the transmission of a randomly large number of distinct biological informations by re-using the same fluorescence channel after bleaching for the transmission of another biological information using the same dye which is conjugated to another specific probe, a.s.o. Thereby noise-reduced quasi-multichannel fluorescence images with reproducible physical, geometrical, and biophysical stabilities are generated. The resulting power of combinatorial molecular discrimination (PCMD) per data point is given by 65,536k, where 65,536 is the number of grey value levels (output of a 16-bit CCD camera), and k is the number of co-mapped biomolecules and/or subdomains per biomolecule(s). High PCMD has been shown for k = 100, and in principle can be expanded for much higher numbers of k. In contrast to traditional multichannel–few-parameter fluorescence microscopy (panel a in the figure) high PCMDs in an ICM lead to high functional and spatial resolution (panel b in the figure). Systematic ICM analysis of biological systems reveals the supramolecular segregation law that describes the principle of order of large, hierarchically organized biomolecular networks in situ (toponome). The ICM is the core technology for the systematic mapping of the complete protein network code in tissues (human toponome project). The original ICM method includes any modification of the bleaching step. Corresponding modifications have been reported for antibody retrieval and chemical dye-quenching debated recently. The Toponome Imaging Systems (TIS) and multi-epitope-ligand cartographs (MELC) represent different stages of the ICM technological development. Imaging cycler microscopy received the American ISAC best paper award in 2008 for the three symbol code of organized proteomes.
3Scan, Inc. was an American biotechnology company based in San Francisco, California which was acquired in 2019, when 3Scan became a part of Strateos. It offered automated microscopy services using a coordinated combination of both hardware and software for the 3D analysis of cells, tissues, and organs. The company was founded in 2011 by Todd Huffman, Megan Klimen, Matthew Goodman, and Cody Daniel. The 3Scan technology is based on the Knife Edge Scanning Microscope developed in the late 1990s by Bruce McCormick, founder of the Brain Networks Lab at Texas A&M University.
Ronald S. Weinstein was an American pathologist. He was a professor at the University of Arizona College of Medicine-Tucson. Weinstein served for 32 years as an academic pathology department chair, in Chicago, Illinois and then Tucson, Arizona, while also serving as a serial entrepreneur engaged in university technology transfer.
Tissue image cytometry or tissue cytometry is a method of digital histopathology and combines classical digital pathology and computational pathology into one integrated approach with solutions for all kinds of diseases, tissue and cell types as well as molecular markers and corresponding staining methods to visualize these markers. Tissue cytometry uses virtual slides as they can be generated by multiple, commercially available slide scanners, as well as dedicated image analysis software – preferentially including machine and deep learning algorithms. Tissue cytometry enables cellular analysis within thick tissues, retaining morphological and contextual information, including spatial information on defined cellular subpopulations. In this process, a tissue sample, either formalin-fixed paraffin-embedded (FFPE) or frozen tissue section, also referred to as “cryocut”, is labelled with either immunohistochemistry(IHC) or immunofluorescent markers, scanned with high-throughput slide scanners and the data gathered from virtual slides is processed and analyzed using software that is able to identify individual cells in tissue context automatically and distinguish between nucleus and cytoplasm for each cell. Additional algorithms can identify cellular membranes, subcellular structures and/or multicellular tissue structures.
