If there were a few extra chapters in Jonathan Swift’s classic tale, Gulliver might have eventually stumbled upon the world's smallest Bible. Even Lilliputians, however, might have had trouble reading this Holy Scripture. The world's tiniest Old Testament is made from 20-nm layers of gold on silicon using focused ion beam technology. More than 300,000 words are inscribed in a space that might fit inside a dot on a traditional Torah scroll. The ion beam used by the team of researchers at Technion Institute of Technology in Haifa, Israel, shot gallium ions, focusing the charged particles on the substrip of gold. The beam dug little holes and each hole is a pixel, which can be filled with information. According to the team who made the tiny book, it’s a record-holder for information density, holding dots just 14-nm big. Unfortunately, extremely expensive equipment is required to read it.

According to Ohad Zohar, a student at Technion, the miniaturization was done as part of a massive educational program aimed at high school students to explain different methods of storing information and spark an interest in nanotechnology.

“The current technology is predicted to continue shrinking and doubling capacity for many years until some ultimate limitation is reached,” Zohar says. “Storing the same amount of information will take four times this area on a modern hard disk, and about 140 times this area on a triple layer DVD. Our nano-bible is [currently] a record holder. But in the future we can think about putting information, one bit per atom, on a substrip. On our Bible, we used 14-nm dia for the smallest dot we had. So if we use an atom, the diameter will be only one tenth of a nanometer—two hundred times smaller. This is interesting. It is 160,000 times denser than our Bible.”

http://www.israelnationalnews.com/News/News.aspx/124713

SOURCE: Israel National News


Measuring molecules in motion
In 1999, California Institute of Technology chemist Ahmed Zewail was awarded the Nobel Prize in Chemistry for his pioneering studies of super-fast reactions. Now a one-of-a-kind electron microscope has been interfaced with an ultrafast laser at Caltech to capture 4-D pictures (3-D molecular structural changes over time) as molecules form and break apart in femtoseconds.

The team has been able to see channels open and close in semiconductor crystals, a phenomenon that has never before been seen. The towering, modified transmission electron microscope that allowed them to see so closely over time is interfaced to an expansive tabletop femtosecond-timed laser system, which requires researchers and visitors to wear safety glasses with dark lenses. Part of the laser beam is used to excite the sample, and the remainder is converted to femtosecond pulses, which result in single-electron packets suitable for probing molecular structures. Because electrons repel each other, single electrons are critical to achieving atomic-scale femtosecond time resolution, Zewail explains. Instead of bringing in all of the electrons at once and having them repel each other, as in some conventional electron microscopes, electrons come in one at a time in the ultrafast electron microscope.

When a single electron bounces off the excited sample in the microscope and hits the instrument's detector, the lenses inside the microscope magnify the object into a single frame that represents the femtosecond resolution and appears as an image on a computer screen. The process of acquiring frames is sequential, and the researchers can put all of the frames together to make a digital movie of what is happening on the atomic level.

http://pubs.acs.org/cen/science/85/8552sci1.html

SOURCE: American Chemical Society


Decoding DNA directly?


Scientists at the Institute for Analytical Sciences in Germany have directly sequenced genetic code in RNA using Raman spectroscopy and atomic force microscopy (AFM). Direct sequencing means the letters of the genetic code are read directly, without onerous analytical techniques. Steered by the AFM, a tiny tip moves over the RNA strand as a laser excites the section being examined. The Raman spectrum of the scattered light gives precise information about the molecular structure of the section. The researchers hope eventually to do the same with DNA.

The new approach builds on earlier efforts to recruit scanning tunnelling microscopy (STM) into the array of available tools. STM, however, provides only low contrast and usually needs a detailed statistical analysis to obtain any useful data. Higher contrast is possible with atomic force microscopy (AFM), the team asserts. They have now combined the near-field prowess of AFM, which allows them to investigate and even manipulate a material at the surface level atom-by atom, with Raman spectroscopy to reveal the details along an RNA strand.

The combination of AFM and Raman, exploits the advantages of both techniques will side-stepping the common low contrast of other microscopy techniques and compensating for the poor lateral resolution of Raman by provide atomic level control.

http://www.spectroscopynow.com/coi/cda/detail.cda?chId=6&id=17959&type=Feature&page=1

SOURCES: Spectroscopy Now; Institute for Analytical Sciences


Hugging the Earth


A new kind of Scanning Transmission Electron Microscope at the Daresbury Laboratory, UK, may pave the way for breakthroughs in medicine, materials and electronics. SuperSTEM 2 advances traditional STEM techniques with a computer-controlled system that corrects for imaging defects. It delivers sharp images of atoms at 20 million times their size; if people were magnified by this much they would be able to hug the Earth!

Built on sandstone bedrock, the incredibly stable geological conditions at the Daresbury Laboratory is one of the key reasons for its location—the system is so stable that any sample in the microscope would move no more than half a millimeter in 100 years. In other words, 2,000 times slower than continental drift.

http://www.scitech.ac.uk/PMC/PRel/STFC/SStem.aspx

SOURCE: Science and Technology Facilities Council


Nipping HIV in the bud


UCLA researchers have found that a key protein in the body's dendritic cells can stop the virus that causes AIDS from "budding", which refers to the part of the virus’ life cycle that is crucial to its ability to replicate and infect other cells. Though dendritic cells can be infected with HIV and play a crucial role in transmitting the virus to T cells, studies have shown that viral generation from these cells is nearly a hundred times lower than from infected T cells, indicating that the cells may possess some inhibiting property.

http://newsroom.ucla.edu/portal/ucla/ucla-researchers-find-cell-protein-42657.aspx


The TEAMwork continues


The Transmission Electron Aberration-corrected Microscope (TEAM 0.5) has recently been installed at the Department of Energy's National Center for Electron Microscopy at Lawrence Berkeley National Laboratory. The latest version of the instrument has achieved a resolution of 0.5 Angstroms (0.05 nm)—a fourth of the diameter of a carbon atom.

Like some high-end commercially available electron microscopes, the TEAM 0.5 uses spherical aberration correction both in the “probe” beam (the electron beam before it strikes the sample) and the image beam (after it exits the sample, but before it reaches the detector). However, the TEAM I will also correct chromatic aberration in the image beam, which has never been accomplished before. Spherical aberration is caused by the shape of a lens; chromatic aberration results when a lens refracts light or electrons of different wavelengths (different colors or energies) at different angles.

"Correcting chromatic aberration is harder and takes more space," says Dahmen. "The chromatic aberration corrector will add two feet to the height of the TEAM I column. But the new configuration will also allow us to enlarge the gap between the pole pieces, into which the sample fits. In TEAM 0.5 this gap is only about 2 mm, so we have to use traditional outside-mounted sample stages, with limited space to manipulate the sample. In TEAM I the gap will be 5 mm; the sample stage will have much greater freedom of movement."

http://www.lbl.gov/Science-Articles/Archive/MSD-NCEM-TEAM05.html

SOURCE: Lawrence Berkeley National Laboratory


Nano-laser offers a new vision


Researchers at the Univ. of California, Berkeley, and the Lawrence Berkeley National Laboratory have developed a laser smaller than a red blood cell that can be tuned to emit different colors. They have incorporated the nanowire-based laser into a device that, by combining features from multiple microscopy techniques, could reveal new details about the structure and behavior of living cells.

http://www.technologyreview.com/Nanotech/18989

SOURCE: Massachusetts Institute of Technology’s Technology Review


New microscope emulates Homer’s cyclops


A low-cost microscope from Celestron puts odd-looking twist on the traditional biological compound microscope. A single "eye" is fitted to the head—that is, a 3.5-inch color LCD screen where the eyepieces ordinarily would go. The instrument has a built-in 2-megapixel digital camera and a USB cable for transferring images to a PC. Images can also be saved on a memory card.

http://www.celestron.com/c2/product.php?CatID=31&ProdID=516

SOURCE: Celestron




Nikon’s new confocal systems add resonant scanner option


Nikon Instruments offers the A1 series of confocal laser point scanning systems, which integrate smoothly with the new Ti-E research inverted microscope. The fully-automated confocal imaging system captures confocal images at high speed with enhanced sensitivity. Designed for facilities with a broad range of users, the A1 line includes the A1R, which uses a resonant scanner with a resonance frequency of 7.8 kHz to achieve high-speed imaging at 230 fps (512 x 64 pixels). In addition, the field of view of scanned area is about five times larger than that of the non-resonant scanner. Two models are available—the fully automated A1 and the high specification A1R. The A1 utilizes conventional paired galvonometers producing high resolution images (up to 4096 x 4096 pixels); the A1R incorporates a hybrid scanner system (offering frame rates of 30 fps, 512 x 512 pixels). The hybrid scanner enables simultaneous photo-activation and imaging, critical for unveiling cell dynamics and interactions.

www.nikoninstruments.com

SOURCE: Nikon Instruments


Who Needs Paris?


Aahhh, April in San Diego. Join more than 13,000 multi-disciplinary scientists at a meeting focused on Experimental Biology, April 5-9. Stay on in the balmy climes to see the latest in new microscopy techniques at the American Association for Cancer Research, to be held there April 12-16.

www.faseb.org
www.aacr.org

- When soft is hard to take
- Harry Potter's invisibility cloak—for real
- IPS cells: an alternative to stem cells?
- Nano-mechanical mapping
- Vee Gee Wiz
- X-ray vision
- Titan Cubed
- Dreaming of genie?
- Gettin' there faster with CARS
- CSI, eat your heart out

When soft is hard to take


A team of Univ. of California, Los Angeles, scientists has differentiated metastatic cancer cells from normal cells in patient samples using leading-edge nanotechnology that measures the softness of the cells. The research team used an atomic force microscope to touch and measure cell softness, and learned that cancer cells are softer than healthy cells. According to UCLA professor James Gimzewski, it is a little like gently squeezing a tomato in the market to see if it’s rotten.

The study, published online edition of the journal Nature Nanotechnology, represents one of the first times researchers have been able to take living cells from cancer patients and apply nanotechnology to analyze them and determine which were cancerous and which were not. The nano-science measurements may provide a potential new method for detecting cancer, especially in cells from body cavity fluids where diagnosis using current methods is typically very challenging. The method also may aid in personalizing treatments for patients.

When cancer is becoming metastatic, or invading other organs, the diseased cells must travel throughout the body. Because the cells need to enter the bloodstream and maneuver through tight anatomical spaces, cancer cells are much more flexible, or softer, than normal cells. These spreading, invading cancer cells can cause a build-up of fluids in body cavities such as the chest and abdomen. But fluid build-up in patients does not always mean cancer cells are present. If the fluid could be quickly and accurately tested for the presence of cancer, oncologists could make better decisions about how aggressive a treatment should be administered or if any treatment is necessary at all.

In this study, researchers collected fluid from the chest cavities of patients with lung, breast and pancreatic cancers, a relatively non-invasive procedure. One problem with diagnosing metastatic disease in this setting is that cancer cells and normal cells in body cavity fluids look very similar under an optical microscope, says Jian Yu Rao, a researcher at UCLA's Jonsson Cancer Center, an associate professor of pathology and laboratory medicine and one of the study's senior authors. Conventional diagnostic methods detect about 70% of cases where cancer cells are present in the fluid, missing about 30% of cases.

"We detect cancer cells typically by looking at them under a microscope after the cells are fixed and stained with chemicals, which is really an antiquated method," Rao says. "Usually the cancer cells have larger nuclei and other subtle features. However, the normal cells from body cavity fluids can look almost identical to cancer cells under an optical microscope. While staining for tumor protein markers could increase diagnostic accuracy, what we were missing was a way to determine if cancer cells have different mechanical properties than normal cells."

The research team used an atomic force microscope to measure cell softness. Because the cells being analyzed were less than half the diameter of a human hair, researchers needed a very precise and delicate instrument to measure resistance in the cell membrane, said James Gimzewski, professor of chemistry and biochemistry, a member of the California NanoSystems Institute and also one of the study's senior authors.

"We had to measure the softness of the cell without bursting it," Gimzewski says. "Otherwise, it's like trying to measure the softness of a tomato using a hammer."

The AFM uses a minute, sharp tip on a spring to push against the cell surface and determine the degree of softness. Think of it as an extension of a doctor's hands performing a physical examination to determine disease, Gimzewski says.

"You look at two tomatoes in the supermarket and both are red. One is rotten, but it looks normal," Gimzewski says. "If you pick up the tomatoes and feel them, it's easy to figure out which one is rotten. We're doing the same thing. We're poking and quantitatively measuring the softness of the cells."

After probing a cell, the AFM assigns a value that represents how soft a cell is based on the resistance encountered. What the team found was that the cancer cells were much softer than the normal cells and they were similarly soft with very little variation in gradation. The normal, healthy cells from the same specimen were much stiffer than the cancer cells and, in fact, the softness values assigned to each group did not overlap at all, making diagnosis using this nanomechanical measurement easier and more accurate.

Researchers next will explore whether the nanomechanical analysis can be used to personalize cancer treatment based on the characteristics of a patient’s cancer cells.

http://www.chem.ucla.edu/dept/Faculty/gimzewski/nnano.html

SOURCE: Univ. of California, Los Angeles


Harry Potter's invisibility cloak—for real

Every child’s dream—of owning an invisibility cloak like Harry Potter's—is one step closer to reality. A research team at the Univ. of Maryland used plasmon technology to create the world's first invisibility cloak for visible light. Generally speaking, when we see an object, we see the visible light that strikes the object and is reflected. The invisibility cloak refracts light, so the light moves around and past the cloak, reflecting nothing and leaving the cloak and its contents "invisible." The research team has used plasmonics to develop superlens microscopy technology.
http://www.reuters.com/article/pressRelease/idUS159108+18-Dec-2007+PRN20071218



IPS cells: an alternative to stem cells?


MIT researchers have treated mice with sickle-cell anemia, beginning by reprogramming the mice's own cells to an embryonic-stem-cell-like state, without the use of eggs. This is the first proof-of-principle of therapeutic application in mice of directly reprogrammed induced pluripotent stem (IPS) cells, and demonstrates the potential of IPS cells to evade the ethical and practical issues raised by embryonic stem cells.

http://web.mit.edu/newsoffice/2007/sickle-cell-1207.html


Nano-mechanical mapping


The National Institute of Standards and Technology (NIST) has developed an imaging system that quickly maps the mechanical properties of materials—how stiff or stretchy they are, for example—at scales on the order of billionths of a meter. The nano-mechanical mapper transforms an atomic force microscope's normal topographical maps of surfaces into precise two-dimensional representations of mechanical properties near the surface.

http://news.thomasnet.com/companystory/538130


Vee Gee Wiz

The XLi-M microscope camera from Vee Gee Scientific produces high-definition documentation and archival of laboratory specimen images and videos. Equipped with 1.3-cm CMOS image sensors, the cameras deliver sharp, bright images. The camera can operate up to 10 fps in full resolution mode, or up to 40 fps in low resolution mode.

http://www.veegee.com/pdf/XLi_M-Series.pdf








X-ray vision


Horiba Jobin Yvon now offers x-ray fluorescence (XRF) microscopes with improved sensitivity, motorized XYZ control, vacuum options and a new dedicated acquisition and analysis software package. XRF microscopy is widely used for elemental analysis in applications as varied as forensic science, pharmaceuticals, geology, museums, electronics and life sciences. Qualitative and quantitative characterization of particles and features less than 10 µm in size is possible.

http://news.thomasnet.com/fullstory/519888


Titan Cubed


Titan3 takes the capabilities of FEI's powerful Titan S/TEM microscope, introduced in 2005, to a new level of performance. Called Titan Cubed because of its fully enclosed profile, it reduces environmental interference, a feature which results in greater stability for better results. The design marks the first time FEI has included as standard the combination of two Cs-abberation correctors and a monochromator on a single instrument.

http://www.feicompany.com/


Dreaming of genie?


DALSA has four new color models in its Genie family of GigE Vision compliant digital cameras designed for industrial imaging applications. These area scan cameras feature resolutions ranging from VGA to 1.4 MP and operate at up to 64 fps in full resolution. The Genie color cameras also feature white balancing and advanced Bayer conversion.

http://www.dalsa.com/mv/news/genie_color.


Gettin' there faster with CARS


Coherent Anti-Stokes Raman Scattering (CARS) microscopy is one the fastest-growing new methodologies for bio-imaging, thanks to recent improvements in detection sensitivity, theoretical understanding of the contrast mechanism and laser sources. CARS permits noninvasive 3-D imaging of live cells based on the vibrational contrast intrinsic to a cell's molecular species. Scientists can attend a CARS workshop at Harvard this summer to learn more.

http://bernstein.harvard.edu/events/carsworkshop.html


CSI, eat your heart out


The JEOL CarryScope is designed for the mobile crime lab where imaging and analysis of trace evidence are conducted right at the crime scene. In research or manufacturing settings, the CarryScope can be transported between the lab, conference room and office. Standard features include 8X to 300,000X imaging and up to 5.0 nm resolution. The optional eucentric motorized specimen stage holds a specimen up to 15.2 cm dia.

http://www.jeolusa.com

- Crowd Control: MIT laser beam “firehose” sorts cells by the thousands
- Zen and the art of microscopy
- Never too early to see art in science
- Reality TV with cells as stars
- National park microscopy
- MicroEuro
- Titan cubed
- Dreaming of genie?
- Gettin' there faster with CARS
- Taking the LEAP

Crowd Control: MIT laser beam “firehose” sorts cells by the thousands

Separating particular kinds of cells from a sample could become faster, cheaper and easier thanks to a new system developed by MIT researchers that involves pushing up the cells with a laser beam its inventors compare to a miniature firehose. When used in tandem with special traps in a silicone layer, the system can sort up to 10,000 cells on a conventional glass microscope slide.

This creative solution to mass organization of biological samples could enable a variety of novel research projects that before might not have been feasible. It could also find applications in clinical testing and diagnosis, genetic screening and cloning research, all of which require the selection of cells with particular characteristics for further testing.

Joel Voldman, an associate professor in MIT's Department of Electrical Engineering and Computer Science, and Joseph Kovac, a graduate student in the department, developed the new system, which is featured in a December cover story in the journal “Analytical Chemistry”.

Present methods allow cells to be sorted based on whether or not they emit fluorescent light when mixed with a marker that responds to a particular protein or other compound. The new system allows more precise sorting, separating out cells based not just on the overall average fluorescent response of the whole cell but on responses that occur in specific parts of the cell, such as the nucleus. The system can also pick up responses that vary in how fast they begin or how long they last.

"We've been interested in looking at things inside the cell that either change over time, or are in specific places," says Voldman. Separating out cells with such characteristics "can't be done with traditional cell sorting."

For example, if cells differ in how quickly they respond to a particular compound used in the fluorescent labeling, the new system would make it possible to "select out the ones that are faster or slower, and see what's different," says Voldman, who also has appointments in MIT's Research Laboratory of Electronics and the Microsystems Technology Laboratories.

He added that the process seems like it should be easy, but it’s not. Other ways of accomplishing the same kind of cell separation exist, but they require complex and expensive equipment, or are limited in the number of cells they can process.

The new system uses a simple transparent silicone layer bonded to a conventional glass microscope slide. Fabricated in the layer are a series of tiny cavities, or traps, in which cells settle out after being added to the slide in a solution. Up to 10,000 cells could be sorted on a single slide.

Looking through the microscope, either a technician or a computerized system can check each cell to determine whether it has fluorescence in the right area or at the right time to meet the selection criteria. If so, its position is noted by the computer. At the end of the selection process, all of the cells whose positions were recorded are then levitated out of their traps using the pressure of a beam of targeted light from a low-cost laser. A flowing fluid then sweeps the selected cells off to a separate reservoir.

The laser levitation of the cells acts like "a fire hose pushing up a beach ball," says Voldman. But the laser method is gentle enough that the living cells remain viable after the process is complete, allowing further biological testing.

Voldman and Kovac are continuing to refine the system, working on making it easier to use and on improving its ability to keep samples sterile. Voldman says that unlike expensive separation techniques such as optical tweezers, the new system could cost only a few thousand dollars. As a result, it could be employed in a variety of biological research laboratories or clinical settings, not just in big, centralized testing facilities.

The research was funded by the National Institutes of Health and the Singapore-MIT Alliance.

SOURCE: Massachusetts Institute of Technology



Zen and the art of microscopy


Sometimes, choice is a burden. Cases in point: the buttons on a typical high-definition TV remote, the listings on eBay, and the mall at Christmastime. There’s just too much to choose from. The same can be said of advanced laser scanning microscopes, many of which are daunting in the amount and complexity of the image acquisition and microscope controls available. Even in integrated microscope control and imaging applications, learning to control the microscope, drive external accessories, manage the digital acquisition process, manipulate the resulting images and store the results can be a substantial barrier to both beginners and advanced users.

Carl Zeiss has launched a new suite of digital imaging software that addresses this problem. The company’s Zen 2007 interface aims to provide a clearly defined user interface that can be individually tailored to each experiment and user. All laser scanning microscopes in the Zeiss LSM 5 Family from release 2.8 onwards can be upgraded to use the new software.

Zen accomplishes its mission by switching between “basic” and “professional” mode in response to user input and, therefore, allows users to focus their full attention on the specimen.

The Zen user interface is customizable and organized into three zones that follow the typical workflow of experiments. Image acquisition and microscope control tools are on the left, the central worktable for image viewing takes up the majority of the screen and file management tools sit on the right. The left toolbar automatically adapts to each user’s personal requirements and can be decoupled and freely positioned on the screen if required.

Zen’s centre pane is used for displaying and interacting with the acquired image data. The tools are arranged under the image and activate and deactivate as necessary. A number of tools were introduced, including the “exposé” mode, in which images from up to three image containers can be opened simultaneously to allow comparison. In addition to improvements in contrast, the optimization of the screen display for the 30-inch widescreen format creates additional space which is useful for complex experiments in which a large number of tool palettes and view windows are open simultaneously.

For more information go to: www.zeiss.com.

SOURCE: Carl Zeiss



Never too early to see art in science


The winner of Olympus America Inc.’s BioScapes Digital Imaging Competition for 2007 was a scintillating portrait of a mouse’s brain by Jean Livet of Jeff Lichtman's lab at Harvard University.

Not only was the image gorgeous in its colorful splendor, it reflected a new technique in fluorescent imaging that allowed Livet to show the brain in 90 different colors rather than the usual three or four.

That’s in keeping with the spirit of the competition, which has opened its website for the 2008 BioScapes. The event recognizes the finest images of life science specimens captured through light microscopes, using any magnification and any brand of equipment. Many of the winning images reflect the advancing art of microscopy by revealing new information in an informative—and artistically attractive—way.

"Last year, we received more than a thousand images and movies. The quality of the entries was extraordinary, and the stories behind the images were fascinating," says Stephen S. Tang, Ph.D., Olympus America Group vice president and general manager, life science.

The deadline for entries is Sept. 30, 2008, and first prize will be an Olympus microscope or camera equipment valued at $5,000. Nine additional winners will also receive valuable prizes from Olympus. Each person entering can submit up to five movies, images, or image sequences. Entries will include information on the importance or “story” behind the images. Winners will be notified in late October, and publicly announced at an event in December.

Winners of the 2007 BioScapes are now touring the U.S. For more information and to see the winners: http://www.olympusbioscapes.com/gallery/2007/index.html.

SOURCE: Olympus America Inc.



Reality TV with cells as stars

Using cryo-electron tomography, researchers from the European Molecular Biology Laboratory, Heidelberg, Germany, have recently demonstrated how protein building blocks are arranged in a single skin cell. A 3-D image shows details of interactions of molecules that underlie cell adhesion in tissues—a mechanism that has been disputed over decades.

The new image marks the closest ever look at human tissue, using a new technique that could help provide new clues to stop the deadly spread of cancer.

Although 3-D images of a body are now commonplace, the equivalent scan of a cell has been a long-standing goal of scientists. Now, advanced tomography has revealed the molecular building blocks of a single skin cell.

The team focused on a class of proteins called cadherins, which play a key role as a kind of Velcro in enabling cells in skin and other organs to stick together, and which form a barrier for a tumor to overcome before spreading through the body, the most deadly feature of cancer, called metastasis.

The result of their work, the first 3-D image of human skin at molecular resolution, was recently published in the journal “Nature”.

"This is a real breakthrough in two respects," says group leader Achilleas Frangakis. "Never before has it been possible to look in three dimensions at a tissue so close to its native state at such a high resolution. We can now see details at the scale of a few millionths of a millimeter. In this way we have gained a new view on the interactions of molecules that underlie cell adhesion in tissues—a mechanism that has been disputed over decades."

A single cell is about 10 µm across and is too small to study using a conventional light microscope. High-voltage electron microscopes are easily able to achieve this resolution, but the vacuum environment of the sample area of the microscope requires that samples be specially prepared, often with a coating of metal. The ability to image a living cell is just not there using most electron microscopy.

Cryo-electron tomography, however, is the technique of choice for Frangakis and his team. They first froze the cells in preparation for electron analysis. Then using tomography, in which scans at different levels are built up to create a 3-D picture, the team put together a reconstruction of the skin cells which shows the "organs"—organelles—of the cell in different colors: the cadhedrins that stick cells together (sandy brown); the compartment that contains the DNA of the cell (blue), with pores (red); the cell's motorways, microtubules (green); the chemical batteries of the cell, mitochondria (purple); and a protein factory called the endoplasmic reticulum (steel blue).

The team focused on the cadherin proteins that are crucial for the integrity of tissues and organs like the skin and the heart, but also play an important role in the spread of cancers. "We could see the interaction between two cadherins directly, and this revealed where the strength of human skin comes from," says Ashraf Al-Amoudi, who carried out the work on one of his own cells in Dr Frangakis' lab.

According to Al-Amoudi, the trick is that each cadherin binds twice: once to a molecule from the juxtaposed cell, and once to its next-door neighbor. “The system works a bit like specialized Velcro and establishes very tight contacts between cells."

Low levels of one kind of this protein, called E-cadherin, can help predict which patients with early breast cancer will need chemotherapy following surgery. It is not the original breast cancer that kills women but the tumor's spread to other sites. Low levels of E-cadherin indicate a substantially increased risk of metastasis, the spread of cancer that makes the disease difficult to treat.

SOURCE: The Telegraph, UK



National park microscopy


Registration is now open for an intensive course in fluorescence microscopy at the bucolic Mount Desert Island Marine Biological Labs, Acadia National Park, Maine. The session, called Quantitative Fluorescence Microscopy will take place from May 31 to June 6 and will examine the theory, mechanics and applications of fluorescent imaging methods. Also included will be extended practicals featuring specimens supplied by the researchers themselves.

The goal of the course is to provide students with the knowledge and expertise to implement cutting edge microscopic methods within their own laboratories. The power and capability of the light microscope has increased dramatically over the last few years, such that light microscopy is now becoming of central utility in all fields of biological research including cell biology, physiology and molecular biology. This change has been driven by the need to study increasingly sophisticated problems at high spatial and temporal resolution. The advances, principally in the field of fluorescence microscopy have been dependant on the development of entirely new microscopic methodologies coupled to the use of fluorescent proteins, new fluorescent dye technologies, highly sensitive detectors and inexpensive powerful computers.

The course will cover all aspects of this technology from the principals of fluorescence imaging to multidimensional imaging in living cells. For more information, visit http://www.cbi.pitt.edu/qfm/index.html

SOURCE: University of Pittsburgh



MicroEuro


Microscience 2008, to be held from June 23-26, is Europe's largest microscopy and imaging event, and is on track to being biggest ever. Europe's premier international conference and exhibition on the science of microscopy, imaging and analysis in both the life and physical sciences, will be held at Excel in London for four days. It is organized by the Royal Microscopical Society and held biennially.

To learn more about this event visit: http://www.microscience2008.org.uk/ms08/show_link1.asp



Titan cubed


Titan3 takes the capabilities of FEI's powerful Titan S/TEM microscope, introduced in 2005, to new levels of performance and enhanced operation. Called Titan “Cubed” because of its fully enclosed profile, it reduces environmental interference providing greater stability. The design also allows the combination of two Cs-abberation correctors and a monochromator on a single instrument. Formerly, these were only optional add-ons.

For more information, go to the company’s website at http://www.feicompany.com/ or read R&D Magazine’s article about FEI’s new S/TEM solution at RDmag.com: http://www.rdmag.com/



Dreaming of genie?


DALSA Corp. has four new color models in its Genie family of GigE Vision compliant digital cameras designed for industrial imaging applications.

These area scan cameras feature resolutions ranging from VGA to 1.4 megapixels and operate at up to 64 frames per second in full resolution. The cameras are equipped with SONY CCD color sensors and feature white balancing and advanced Bayer conversion.

This GigE Vision integrates advanced camera and board image acquisition technologies in one package, making it suitable for industries such as food processing, automotive inspection, print inspection, pharmaceutical inspection, part presence and/or detection, printed circuit board assembly, Intelligent Traffic Surveillance (ITS), and numerous quality and grading applications.

Based in Waterloo, Ontario, Canada, DALSA is large-scale producer of equipment for the semiconductor industry, and previously marketed versions of the Genie without color. According to DALSA’s vice president of sales and marketing, Philip Colet, the addition of color opens new opportunities for “inspection applications requiring more clarity and distinction. We see many OEMs, comprised of both new and existing clients, updating their systems to now include color.”

All of DALSA’s Genie cameras are certified GigE Vision compliant by the Automated Imaging Association and transmits data over standard CAT-5e and CAT-6 cables to distances of up to 100 m. The devices are supported by Sapera Essential software and its Genie Framework package for quick camera set-up. For additional details visit: http://www.dalsa.com/mv/news/genie_color

SOURCE: DALSA



Gettin' there faster with CARS


Coherent Anti-Stokes Raman Scattering (CARS) microscopy is one of the hottest methodologies for bio-imaging, thanks to recent improvements in detection sensitivity, theoretical understanding of the contrast mechanism and laser sources. CARS allows noninvasive 3-D imaging of live cells based on the vibrational contrast intrinsic to a cell's molecular species.

The popularity of method is such that instructional workshops are being held to help interested parties. A CARS workshop, for example, is being held at Harvard University in June, 2008.

CARS was originally developed to address the need for high-resolution morphological information with chemical specificity. Optical microscopy, though able to probe living specimens with subcellular resolution down to several hundred nanometers, is unable to provide this chemical data. The contrast in confocal reflectance microscopy and optical coherence tomography (OCT), for instance, is based on refractive index differences, and cannot directly probe the chemical composition of tissue structures.

Vibrational spectra of biological specimens contain a multitude of molecular signatures that can be used for identifying biochemical constituents in tissue. Other forms of microscopy, including fluorescence and infrared, have limitations in their ability to be sensitive to these spectra. CARS, a nonlinear Raman technique, is able to attain much stronger vibrational signals. It allows for point-by-point 3-D imaging of thick specimens, similar to two-photon fluorescence microscopy.

To learn more or to participate in the workshop visit: http://bernstein.harvard.edu/events/carsworkshop.html



Taking the LEAP


There are few ways to gauge mass more accurately than by profiling a material atom by atom. Imago, which develops microscopes intended to do exactly that, has released its new LEAP HR family for a wide range of materials research applications. The "HR" designates High (mass) Resolution, to enable the analysis of individual atoms with excellent compositional accuracy in voltage-pulse mode. The LEAP 3000X HR configuration includes laser-based atom probe capability in addition to voltage pulsing.

The configuration allows for precise analysis by removing and examining individual atoms using the combination of a high electrical field and either an ultra-fast voltage pulse or an ultra-fast laser pulse. Each ion is analyzed by measuring the time of flight to the detector through an energy-compensated time-of-flight mass spectrometer.

Imago claims the new 3000X HR has best-in-class mass resolution, and is capable of large field of view of more than 150 mm at this resolution. This, the company says, helps the material’s atomic scale features to be understood in the context of the larger-scale nanostructure.

For more information, visit: http://www.imago.com/imago

- OME gosh, think of the possibilities
- Nikon Launches Ti-E
- Brighter wafer inspection
- Lynx in a 360-degree chain
- New LED system coming to light
- I'd like to order a protein, please


OME gosh, think of the possibilities

The Open Microscopy Environment (OME) has released the OMERO3 application for free management and visualization of digital microscopy data. OME is a multi-site collaborative effort among academic labs and commercial entities, producing open tools to support data management for biological light microscopy.

Research-active labs participating in the OME project are at the Swedlow Lab, Univ. of Dundee, UK; the Goldberg Lab, National Institute on Aging, Baltimore, Md.; the Sorger Lab, Massachusetts Institute of Technology, Cambridge, Mass.; and the Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison. A number of imaging and informatics groups are involved as well.

While many other applications could use OME's architecture and design, the specific implementation is limited to biological microscopy. All OME formats and software are free, and all OME source code is available on the website: www.openmicroscopy.org.

Currently in Beta 2 release, OMERO is a java-based server/client system for visualizing, managing, and annotating microscope images and metadata, and is separated into several components:

• OMERO.server, which supports several remote cross-platform Java clients and is the groundwork application in the OMERO software line;
• OMERO.webadmin, which is a web browser-based server admin tool that replaces the functionality available in the OMERO.admin client application. It is included with the OMERO.server distribution. OMERO.admin has been deprecated and should not be used to configure the OMERO3-Beta2 server.
• OMERO.insight (also known as "Shoola"), the client application used to view, categorize, and annotate images from an OMERO server; and
• OMERO.importer, which can read a wide range of image file formats and upload them into the OMERO server.

All OMERO software is provided in easy-to-install bundles for most operating systems.

SOURCE: Open Microscopy Environment





Nikon Launches Ti-E

Nikon has combined streamlined component automation with speeds more than twice that of previous Nikon inverted microscopes with the launch of the Eclipse Ti-E inverted research microscope. The first wholly new inverted microscope platform from Nikon since the launch of the Te2000 seven years ago, the Ti-E includes Nikon’s Perfect Focus System and high-speed motorization for improved efficiency. Other new features include a "full intensity" external phase contrast system, which is incorporated into the microscope body, rather than in the objective lens.

The Eclipse Ti-E (as well as accompanying Ti-U and Ti-S) provides researchers access to advanced live-cell imaging solutions such as TIRF, confocal, FRET, photoactivation and microinjection. The microscopes use Nikon CFI60 optics and benefits from the latest generation of Nikon-developed software, NIS-Elements.

Among the goals in developing the Ti-E, in addition to improved resolution, was an increase in speed through efficient design and electronic upgrades. Individual motorized components were enhanced—including the joystick and scan stage—and a digital controller hub was introduced. The introduction of firmware inside the microscope has resulted in a reduction in the communication time among various microscope components. For example, the total time for continuous image acquisition in three modes (two-channel fluorescence and phase contrast) with illumination shutter control was greatly reduced. The screening image capture of 96 wells in three modes can now be done at speeds more than twice that of conventional models.

Time-lapse observation is an increasingly popular tool for live-cell researchers, but the enemy has long been focus drift. The Perfect Focus System (PFS) was designed to maintain a crisp image even when reagents are used with high numerical aperture objectives and when techniques such as total internal reflection fluorescence (TIRF) are employed. Real-time correction is the Z-plane is possible with this system, which is part of the firmware installed on the microscope. The PFS can be retracted when not in use. Similarly, multiple optics systems can be installed and retracted from the optical path, part of what Nikon calls “infinity optics”. Possible additions to the stratum structure include the simultaneous use of laser tweezers, photoactivation unit, and multiple epi-fluorescences turrets. This ability opens the door to efficient use of motorized laser TIRF for observations of cell membrane dynamics.

If an optional back port is specified, Förster resonance energy transfer (FRET) can be used for intracellular study. Each FRET channel can be separated by wavelength and sent to separate cameras, enabling the capture of high-resolution images in the entire frame for each wavelength. Nikon also provides imaging solutions for Nomarski differential interference contrast, Hoffman modulation contrast, darkfield and phase contrast that are easily mountable on the Ti-E. A phase ring has been incorporated into the microscope’s body to speed the attachment of high numerical aperture objectives. For more information, visit www.nikoninstruments.com.

SOURCE: Nikon Instruments



Brighter wafer inspection

Olympus is continuing its product development for the semiconductor industry’s 300 mm standard with the introduction of a two-controller system that enables both inspection and analysis in the same unit. The Olympus MX61A 300 mm wafer compatible automatic semiconductor inspection microscope system is designed to use the new high-performance UIS2 objective lenses. The benefit is and increase in brightness in darkfield observation by 4 times. In addition, a newly developed active autofocus system is used to increase efficiency.

This instrument is the top-end model in the Olympus MX series of semiconductor inspection microscopes. The first MX microscopes were sold in 1996, and based on this inheritance, the MX61A has further advanced automation and motorization of microscopic observations.

As wafers have increased in size, the integration density of semiconductor devices fabricated onto wafers has equally increased. The MX series has evolved to handle these requirements. With the advancement of customer technology in the semiconductor device industry, the need to customize microscopic observation methods for each individual customer is increasing.

Furthermore, motorized optical microscopes with high optical and reproduction performance are needed at production sites and for R&D activities.

Key components of the MX61A include:
Dual engines. The “inspection engine” and the “analysis engine” in the MX61A are selectable by the user. The operations unit controls the inspection engine. Observation conditions can be called up through the operation unit at any time, and sharing among multiple operators (observers) is also possible. What controls the analysis engine is the microscope’s control software. This software is capable of operating the microscope, as well as controlling peripheral equipment such as a digital camera or motorized stage.

UIS2 optical system. In brightfield observation, the UIS2 optics retain crisp, natural color reproduction. In darkfield imaging, brightness has been increased by an average of more than four times as compared with prior Olympus UIS series systems.

Autofocus. Automated modules including automatic aperture stop, motorized DIC, active A (Autofocus) create innovative efficiency in observation and digital image documentation. The new U-AFA2M series is a more advanced version of active-type laser autofocus capable of high speed and accuracy. It comprises of VIS (Visible) type and VIS/DUV compatible type. The introduction of a newly developed multi-spot sensor has enabled a substantial increase in autofocus stability by eliminating the influences of vertical topography on the specimen. This allows for faster observations and easier operations.

To learn more, go to:
http://semiconductor.firstlightera.com/EN/Microsites/1/Olympus+Industrial/OlympusNEWAutomaticSemiconductorMicroscope-MX61A.htm

SOURCE: Olympus America Inc.



Lynx in a 360-degree chain

Solder joints and pad alignment can bee difficult to inspect using traditional stereoscopic methods. Vision Engineering is addressing this limitation with the release of an updated Lynx light-emitting diode (LED) stereo microscope with oblique and direct viewer for printed circuit board (PCB) inspection. It provides a full 360-degree view around the PCB for 34-degree angled inspection of solder joints and pad alignment. An added benefit is the bright, long-life white light from LED illumination.The optics in the Lynx are eyepiece-free, a feature which should significantly increase head freedom and eye relief, reducing operator stress and fatigue over long periods of time.

Lynx is used in a wide range of industry applications including general manufacturing, electronics, precision engineering, medical devices, plastics and rubber. The microscope has a 2.1x to 120x stereo zoom magnification in a modular design that allows addition of accessories such as image capture devices.

Additional features include electrostatic discharge protection, and a Lynx VS8 variant designed specifically for a PCB inspection workstation. The Lynx is available with an adjustable, swing-away boom mount for mounting directly to the user’s work surface or with a coated platform base for easy transport. Alternately, a focusable bench stand with subject holder, substage illumination, and floating or measuring stage options is also available.

SOURCE: Vision Engineering, www.visioneng.com



New LED system coming to light

Carl Zeiss incorporates light-emitting diode (LED) technology in the Colibri illumination system designed for widefield fluorescence microscopy. The modular Colibri system employs up to four LED modules, each individually controlled by electrical current without mechanical switching devices. LEDs of different colors can be used in combination, giving users the option of seeing multiple fluorochromes simultaneously or rapidly capturing sequential images of each fluorochrome.

Colibri is part of Zeiss’s efforts to develop increasingly differentiated fluorescence techniques for life science. Colibri’s modules utilize 10 LEDs, ranging from ultraviolet through to dark red, via the full spectrum commonly used in fluorescence microscopy. The desired intensity can be set in percentage steps for each individual LED using a control panel or with the help of the AxioVision system software. The illumination can be adjusted individually depending on the sensitivity of the sample. This prevents bleaching. Each LED can be switched on and off and adjusted in the microsecond range.

Optoelectronics were heavily employed in the Colibri design—no switching mirrors, no mechanical shutters, and no filter wheels are used. Only the current is switched. Switching times in the microsecond range can be achieved between the different LED modules and between the different intensity settings of a single LED.

The possibility of adjusting the intensity in fine steps helps protect living samples, leading to longer observation times. The possibility of freely adjusting the various wavelengths—which can also be employed simultaneously—opens up new possibilities for scientific analysis of fixed samples. Time-consuming and labor-intensive routines, such as searching for a small number of cells with a certain combination of differently labeled proteins, are now simpler.

As is common to LED illumination, very little heat is generated by Colibri microscopy.

Vibrations, noises, and time delays are minimized using optoelectronics, and emission stability from the LEDs is very high. The narrow-band emission of the LEDs means less stray light in the background of the images of your samples. A long lamp life for the LEDs is an added benefit. Via the integrated interface, users can use a white light source coupled using a light guide for applications that are not yet covered optimally by LEDs. The images have a higher dynamic range. Consequently, even the finest structures and the weakest signals can be detected more easily.

Changing the LED modules is straightforward: remove the plug, undo the clamping screw, remove the LED module and insert a new LED. Beam combiner exchanges are also simplified to removing the mounting frame and inserting a new frame. Each LED module is equipped with a component recognition chip that enables the new module to be detected automatically.

Colibri is recommended for use with the Axio Observer, Axiovert 200, Axio Imager, Axioplan 2, Axioskop 2, Axioskop 2 FS and Axioskop 40 System Overview.

To find out more visit: www.zeiss.com/micro.

SOURCE: Carl Zeiss MicroImaging Inc.



I'd like to order a protein, please

Derek Woolfson of the University of Bristol, UK, and colleagues have discovered a way to engineer nanoscale order into protein fibers. Their system has two peptides, which normally co-assemble into thickened protein fibers in water. The result shows a level of order on the nanoscale that mimics certain natural fibrous assemblies. The work is a step toward rational bottom-up assembly of nanostructured fibrous biomaterials for potential applications in synthetic biology and nanobiotechnology.

This system can be rationally engineered to alter fiber assembly, stability, and morphology. The peptides themselves assemble into two-stranded helically-coiled rods, which pack in a 3-D hexagonal lattice of slightly more than 1.8 nm in size, and with a periodicity of 4.2 nm along the fiber axis. The model is supported by both electron microscopy and x-ray diffraction.

Specifically, the fibers display surface striations separated by nanoscale distances that precisely match the 4.2-nm length expected for peptides configured as designed. These patterns extend unbroken across the widths ( 50 nm) and lengths (>10 µm) of the fibers. Furthermore, the spacing of the striations can be altered predictably by changing the length of the peptides. These features reflect a high level of internal order within the fibers introduced by the peptide-design process.

According to Woolfson, this structure—in its exceptional order and persistence along and across fibers—is unique in a biomimetic system.

To learn more about the team's discoveries, visit: http://www.lifesci.sussex.ac.uk/research/woolfson/html/

SOURCE: National Academy of Sciences

The complexity of science

Events Calendar

May 19-22
21st Annual Technical Conference & Exhibition
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10th Annual C21 BioVentures
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June 1-5
56th ASMS Conference on Mass Spectrometry
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June 9-12
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