What Is EMCCD Technology

 

Definition of EMCCD Technology EMCCD technology is a digital scientific detector innovation first introduced to the imaging community by Andor Technology Plc. in early 2000, followed by a spectroscopy version in early 2005. At the time, Andor coined the term ‘Electron Multiplying Charge Coupled Device (EMCCD)’ to amply describe the underlying process that defines this novel new technology platform.* EMCCD is a quantitative digital camera technology that is capable of detecting single photon events whilst maintaining high Quantum Efficiency, achievable by way of a unique electron multiplying structure built into the sensor. Unlike a conventional CCD, an EMCCD is not limited by the readout noise of the output amplifier, even when operated at high readout speeds. This is achieved by adding a solid state Electron Multiplying (EM) register to the end of the normal serial register; this register allows weak signals to be multiplied before any readout noise is added by the output amplifier, hence rendering the read noise negligible. The EM register has several hundred stages that use higher than normal clock voltages. As charge is transferred through each stage the phenomenon of Impact Ionization is utilized to produce secondary electrons, and hence EM gain. When this is done over several hundred stages, the resultant gain can be (software) controlled from unity to hundreds or even thousands of times. * The term has since become the industry standard, used by almost every manufacture and user of this technology. Source of the article above : http://www.emccd.com/what_is_emccd/ ---------------------------------------------------------------------------------------------------------------------------------------------- QuantEM:512SC EMCCD Camera Full Field-of-View Fluorescence Microscopy The QuantEM:512SC is the only scientific camera in the world that offers electron-multiplying (EM) gain with true quantitative stability across 16 bits at 10-MHz, 5-MHz, and 1.25-MHz operation speeds. A linearized and quantitative EM gain slider provides a much more intuitive, easily quantifiable EMCCD camera, while a self-calibrating EM gain feature ensures that the camera delivers the proper amounts of user-specified EM gain and remains quantitative over time. Key Camera Features Datasheets and Technical Resources Imaging Software and Drivers Published Articles and Research Contact Us EMCCD Cameras   |   CCD Cameras   |   Multichannel Imaging Systems   |   Retired Demo Cameras Primary Applications Quantitative FRET Multiprobe Experiments Ratiometric Ion Imaging Confocal Microscopy Live-Cell Fluorescence Imaging source: http://www.photometrics.com/products/emccdcams/quantem.php

An Eye on Imaging Science

 

Fri, 07/31/2015 - 6:45pm Lindsay Hock, Editor Photo: Kodak Kodak has a dedicated team of scientists working to enhance imaging science Image science and technology attracts researchers from academic and government institutions, as well as practitioners in the imaging industry globally. The diverse research interest and the multidisciplinary characteristics of the imaging field encourage competing ideas to be presented and tested by researchers. This, in turn, prompts imaging technologies to quickly respond to challenges from various scientific disciplines. “An example of this can be seen over the past decade, where the main research interest for printing technologies evolved from 2-D image formation on different paper substrates to 3-D digital fabrication for medical and manufacturing applications,” says Dr. Chunghui Kuo, Senior Image Scientist, Eastman Kodak Co. “All of this was directly attributed to the accelerated advancement of telecommunication and digital display technologies.” However, imaging science is as underappreciated as it is pervasive. People often underappreciate scientific advancements they believe as easy to accomplish. This is regardless of the complexity or difficulty behind the discovery. “For example, identifying a specific person in a crowded room is a difficult task in imaging science; but its value is less likely to be recognized,” says Kuo. “Think about it this way: nearly 50% of the cortex in the human brain is related to visual functions, which indicates the type of technological challenges encountered in imaging science.” Yet, recent advancements in visualization, image understanding and 3-D printing have driven significant interest for many topics imaging science research can tackle. Digital imaging technologies have become indispensable in society and are extending to new scientific frontiers to integrate advancements across several fields, including medicine and engineering. The trends With the importance of imaging science and its impact in various scientific fields, trends are developing. One trend is image deposition. And these technologies have extended into high-precision microscopic additive manufacturing processes in biomedical engineering and 3-D fabrication. Virtual reality is also a trend within imaging science, and this pushes beyond the realms of biological aspects into fields such as aerospace, architecture and energy. “The goal of realizing a virtual world indistinguishable from reality is pushing the envelope,” says Kuo. “Virtual reality requires a thorough understanding of the interaction between the physical surface property of the material and human vision system.” Artificial intelligence is also a trend in imaging, and is a buzzword in R&D, especially in robotics and information technology. The ability to recognize an object and understand the meaning of a natural image is the ultimate goal in this space. “This has led to extensive collaboration between the imaging science and computer engineering research communities to get us there,” says Kuo. Ink-jet printing has also received attention in recent years. “Using ink-jet printing technologies to digitally fabricate biologically active structure with high precision has received attention for its potential applications in the fields of medical and biological science,” says Kuo. As medical research continues to progress, researcher have started to explore the possibility of personalized medicine with individual drug release properties by digitally fabricating drug dosage. “In the frontier of additive manufacturing processes, digital printing technologies have demonstrated the capability of fabricating 3-D microscopic structures, indicating great potentials for future industrial applications, for example printing electronics on flexible substrate,” says Kuo. Furthermore, the rapid development in computational science and engineering has empowered complicated visualization algorithms to support the computer graphic industry, with high expectation of the potential of virtual reality technology in the near future. Yet, improvements still must be made to advance digital fabrication technologies to serve as the driving force for the next industrial revolution. “For example, the ability to guarantee the final quality of a digitally fabrication product is vitally important for medical applications,” says Kuo. Also, the microscopic imaging scanning in a 3-D setting not only poses a challenge in image acquisition, but also creates a massive data set that must be stored and analyzed. “The same obstacle exists in spectral and hyperspectral imaging, where spectrum data is collected at each spatial location and time interval,” says Kuo. The broad imaging future “Imaging science and technology is at a unique point to participate in multiple fundamental R&D activities,” says Kuo. And these activities include digital fabrication, virtual reality and artificial intelligence, all of which are considered major driving forces for the next industrial revolution. “I truly believe that the future for imaging technologies is bright, and with our concerted effort, we will be able to have a significant contribution on the lives of future generations,” says Kuo. source : http://www.rdmag.com/articles/2015/07/eye-imaging-science

With light echoes, the invisible becomes visible

 

June 17, 2014

Scientists have developed a novel camera system which can see around the corner without using a mirror. Using diffusely reflected light, it reconstructs the shape of objects outside of the field of view. A laser shines on the wall; a camera watches the scene. Nothing more than white ingrain wallpaper with a bright spot of light can be seen through the lens. A computer records these initially unremarkable images and as the data is processed further, little by little, the outlines of an object appear on a screen.

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Prof. Dr.-Ing. Matthias Hullin from the Institute of Computer Science II at the University of Bonn.

Scientists at the University of Bonn and the University of British Columbia (Vancouver, Canada) have developed a novel camera system which can see around the corner without using a mirror. Using diffusely reflected light, it reconstructs the shape of objects outside of the field of view.

The researchers will be reporting their results at the international Conference for Computer Vision and Pattern Recognition (CVPR) from June 24-27 in Columbus (Ohio, USA).

A laser shines on the wall; a camera watches the scene. Nothing more than white ingrain wallpaper with a bright spot of light can be seen through the lens. A computer records these initially unremarkable images and as the data is processed further, little by little, the outlines of an object appear on a screen. Yet, this object is behind a partition and the camera cannot possibly have seen it -- we have apparently looked around the corner. A magic trick? "No," says Prof. Dr.-Ing. Matthias B. Hullin from the Institute of Computer Science II at the University of Bonn. "This is an actual reconstruction from diffusely scattered light. Our camera, combined with a mathematical procedure, enables us to virtually transform this wall into a mirror."

Scattered light is used as a source of information

The laser dot on the wall is by itself a source of scattered light, which serves as the crucial source of information. Some of this light, in a roundabout way, falls back onto the wall and finally into the camera. "We are recording a kind of light echo, that is, time-resolved data, from which we can reconstruct the object," explains the Bonn computer scientist. "Part of the light has also come into contact with the unknown object and it thus brings valuable information with it about its shape and appearance." To be able to measure such echoes, a special camera system is required which Prof. Hullin has developed together with his colleagues at the University of British Columbia (Vancouver, Canada) and further refined after his return to Bonn. In contrast to conventional cameras, it records not just the direction from which the light is coming but also how long it took the light to get from the source to the camera.

The technical complexity for this is comparatively low -- suitable image sensors came onto the mass market long ago. They are mainly found in depth image cameras as they are used, for instance, as video game controllers or for range measurements in the automotive field. The actual challenge is to elicit the desired information from such time-of-flight measurements. Hullin compares the situation to a room which reverberates so greatly that one can no longer have a conversation with one's partner. "In principle, we are measuring nothing other than the sum of numerous light reflections which reached the camera through many different paths and which are superimposed on each other on the image sensor."

This problem, known as multipath interference, has been giving engineers headaches for a long time. Traditionally, one would attempt to remove the undesired multipath scatter and only use the direct portion of the signal. Based on an advanced mathematical model, Hullin and his colleagues, however, developed a method which can obtain the desired information exclusively from what would usually be considered noise rather than signal. Since multipath light also originates from objects which are not at all in the field of view, the researchers can thus make visible what is virtually invisible.

Minimal technical complexity and intelligent programming

"The accuracy of our method has its limits, of course," says Prof. Hullin -- the results are still limited to rough outlines. However, the researchers assume that based on the rapid development of technical components and mathematical models, an even higher resolution can be achieved soon. Together with his colleagues, he will present the method at the international Conference for Computer Vision and Pattern Recognition (CVPR) from June 24 to 27 in Columbus (Ohio, USA). The new technology is received with great interest -- Hullin hopes that similar approaches can be used, for example, in telecommunications, remote sensing and medical imaging.

New imaging technology: Phase contrast x-ray

 

The researchers have succeeded in advancing an emerging imaging technique for breast investigations: the X-ray phase-contrast mammography. The new developments enable distinguishing between the different types of microcalcifications observed in breast tissue and help assigning them to malignant lesions. The study has just been published in Nature Communications.

One of the advantages of the phase contrast technique is its ability to provide images of high contrast. In the future, this technique can aid physicians to determine in a non-invasive way where premalignant and malignant breast lesions are most likely located. One goal of breast cancer screening is to detect (groups of) microcalcifications in the breast, because these may be associated with early stages of breast cancer since they often occur in connection with cancer cell death. Mammographic screening does not allow definite conclusions regarding the underlining conditions that cause calcifications. Only tissue biopsies that are examined under the microscope by pathologists can determine which lesions have caused the calcareous deposits.

Clinical equipment could be used for phase contrast imaging

At the PSI, the use of phase contrast for medical X-ray imaging has been investigated for several years. X-ray radiation as used in conventional mammography was long considered not suitable for phase contrast procedures because of its incoherence and mixture of multiple wavelengths. "The fact that we have now managed to use these X-ray sources for the phase contrast method in order to develop a new and improved imaging method is a considerable step towards application in daily clinical practice," says Marco Stampanoni, Professor at the Institute for Biomedical Engineering at ETH Zurich and Head of the X-ray Tomography Group at the PSI. He received an ERC Consolidator Grant in 2012 to advance the clinical use of X-ray phase contrast.

In X-ray phase contrast, the extent in which tissue absorbs x-rays is not the only quantity that is being measured but also how tissue deflects radiation laterally (refraction) and consequently how it influences the sequence of oscillation peaks and valleys of X-ray waves -- the so-called phase. Depending on the tissue type, the overall scattering also varies. To be able to measure the phase shift, researchers use three very fine grids. The first one is located directly at the source. It ensures that the object is illuminated with the required coherence. Another grid is placed behind the object and generates an interference signal that is analyzed by a third grid downstream. Using suitable algorithms, the re-searchers calculate the absorption, phase and scattering properties of the object from the interference signal. This information can be used to generate sharp and high-contrast images that show very detailed soft tissue properties. A discovery by Zhentian Wang, PostDoc in Prof. Stampanoni's team, initiated this development: "During my trials with the phase contrast method, I noticed that there are microcalcifications with different absorption and scattering signals. That indicated that the new method might identify different types of calcifications," he says. Wang subsequently reviewed through medical literature and found studies that showed that a certain type of calcification is more frequently associated with breast cancer precursors. "I was persuaded that my observation could be very interesting for breast cancer diagnosis, since it could distinguish between the different types of microcalcifications," says the researcher.

Clinically relevant

The relevance of the new method was also confirmed by the physicians who participated in the study: "We are hopeful that the new technique, in comparison to standard mammography, will help to better indicate where a biopsy must be carried out in the breast," says Rahel Kubik, Head of the Institute of Radiology at the Kantonsspital Baden. "Still, it is not ready for clinical use as it needs to be validated in a larger number of cases," says the radiologist. "But it is very encouraging that the new method enables a distinction between the different well-known microscopic types of calcifications," confirms Gad Singer, Head of the Institute of Pathology at the Kantonsspital Baden.

Whether the technology will make it to clinical use also depends on the radiation dose. "The aim will be to significantly improve quality, resolution and diagnosis with the same radiation dose as for a standard mammography so that breasts can be better examined" says Nik Hauser, Head of Gynaecology and of the Interdisciplinary Breast Center at the Kantonsspital Baden. "If we can significantly improve imaging, this would enable better assessments of tumor extent prior to surgery. Then the new method will quickly become important," he is convinced. The foundation for a new imaging device has been laid, says Hauser. "We are optimistic that we soon will be able to present further results." To date, the re-searchers have worked with a prototype. They examined breast tissue samples, but no patients have been involved yet. "One of our next aims will be to develop a device for clinical use," says Marco Stampanoni.

Weak chemical forces combined to strengthen novel imaging technology

 

May 21/ 2014

Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Increasing the effectiveness of certain contrast agents is often used for imaging blood vessels and internal bleeding by associating them with nanoparticles, biomedical researchers report. The contrast agent being used is packaged inside or bonded to the surface of microscopic particles, which can be designed to target certain regions of the body or prolong the agent's activity.

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Kong and others demonstrated that their fastener molecule readily inserted itself into the membrane of pre-made liposomes. Gadolinium stably associated with the modified nanoparticles in solution, and experiments in animal models showed that these nanoparticles produced clear diagnostic images.

When Associate Professor of Chemical and Biomolecular Engineering Hyunjoon Kong, graduate student Cartney Smith, and colleagues set out to improve MR imaging (MRI), they turned current contrast agent technology on its head -- or rather, they turned it inside out. The new compound they designed in collaboration with Roger Adams Professor of Chemistry Steven C. Zimmerman is not only more effective, but also self-assembling. Kong is a member of the Regenerative Biology and Tissue Engineering research theme at the Institute for Genomic Biology.

When doctors perform an MRI, they administer a contrast agent: a chemical that, when injected into the bloodstream or ingested by the patient just before the MRI, improves the clarity of structures or organs in the resulting image. One common class of contrast agent, often used for imaging of blood vessels and internal bleeding, contains gadolinium, a rare-earth metal.

Recently, biomedical researchers have found ways to increase the effectiveness of certain contrast agents by associating them with nanoparticles. The contrast agent being used is packaged inside or bonded to the surface of microscopic particles, which can be designed to target certain regions of the body or prolong the agent's activity.

Researchers are now exploring the multipurpose use of nanoparticles. If particles could be loaded with several types of contrast agents or dyes instead of one, or a contrast agent along with another type of diagnostic aid or a medication, doctors could more efficiently test for and treat conditions, and limit the number of injections received by patients.

Just like toddlers sharing a new toy, though, compounds packaged together into a nanoparticle cannot always play well together. For example, contrast agents may bind to other chemicals, reducing their effectiveness. In addition, when contrast agents are enclosed inside a nanoparticle, they may not work as well. Attempts to attach agents to the outer surface of nanoparticles via covalent formation are also problematic, as they can negatively affect the activity of the nanoparticles or the compounds that they carry.

Kong, Smith and colleagues tackled these challenges by using interactions between naturally occurring biomolecules as a guide. Many types of proteins are strongly attached to cell membranes not by covalent bonds, but by the sum of multiple weaker forces -- the attraction of positive and negative charges, and the tendency of non-polar (oil-like) substances to seek each other and avoid water.

The group hypothesized that the same types of forces could be used to attach a contrast agent to the surface of a type of nanoparticle called a liposome, which resembles a little piece of cell membrane in the shape of a tiny bubble. The researchers designed a "fastener" molecule, DTPA-chitosan-g-C₁₈, that is charged, attracting it to the liposome and binding it to the contrast agent gadolinium. A nonpolar region anchors it to the liposome membrane.

In a series of experiments reported in a recent ACS Nano article, Kong and others demonstrated that their fastener molecule readily inserted itself into the membrane of pre-made liposomes. Gadolinium stably associated with the modified nanoparticles in solution, and experiments in animal models showed that these nanoparticles produced clear diagnostic images.

"The strategy works like Velcro on a molecular level to adhere functional units to the outer leaflet of a liposome," said Smith, who was first author on the study. "This work represents a new material design strategy that is scalable and easily implemented. The development of improved contrast agents has the potential to directly impact patients' lives by detecting damaged blood vessels."

One of the difficulties of working with liposomes is their tendency to degrade inside the body. When the fastener-loaded liposomes degraded, some of the efficacy of the gadolinium was lost. In a second study published in Langmuir (DOI: 10.1021/la500412r), Kong and Smith developed a process for chemically cross-linking the components of the nanoparticle that prolonged the life of the nanoparticles in biological conditions.

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Story Source:

The above story is based on materials provided by Institute for Genomic Biology, University of Illinois at Urbana-Champaign. The original article was written by Claudia Lutz. Note: Materials may be edited for content and length.

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Journal Reference:

1. Cartney E. Smith, Hyunjoon Kong. Cross-Linkable Liposomes Stabilize a Magnetic Resonance Contrast-Enhancing Polymeric Fastener. Langmuir, 2014; 30 (13): 3697 DOI: 10.1021/la500412r