Olympus licenses digital pathology patents to BioImagene, Inc.

Olympus America Inc. has signed a nonexclusive worldwide licensing agreement with BioImagene, Inc. of Sunnyvale, California, allowing BioImagene to access an extensive portfolio of Olympus patents in the field of digital pathology and virtual microscopy. This is the most recent of several licenses that Olympus has granted for the technologies, which are considered critical for developing future digital imaging and data handling systems for pathology.

Digital pathology technology has the potential to change the way doctors review and manage millions of biopsy slides and other pathology specimens now handled using glass slides and traditional optical microscopes. The patents included in the licensing deal cover methods and equipment for creating, storing and delivering virtual microscopy slides. The technology enables pathologists to view and share high-resolution virtual microscopy images over the Internet.

The companies are not making specific terms and conditions of the agreement public.

Zero Drift Inverted Microscope with Autofocus

Olympus has introduced the new IX81-ZDC2 Zero Drift microscope system, a motorized inverted microscope with a comprehensive, integrated autofocus solution for investigators doing time-lapse experiments. The system’s autofocus system is designed to operate continuously so that it maintains focus even when the events being observed happen very quickly and experiments occur over a short timescale.

In addition, the system easily can be set to operate in a discrete, one-shot mode designed to facilitate applications that require maintaining multiple focus positions, such as experiments involving multi-well imaging. The system is optimized for use with total internal reflectance fluorescence (TIRF) and other advanced applications.

The ZDC2 Zero Drift system uses a Class 1 785-nm laser diode to locate either the water/glass interface (for oil- or water-immersion objectives) or the air/glass interface (for non-immersion lenses). Samples can be mounted on coverslips, multi-well tissue culture plates, glass-bottom culture dishes or other glass substrates. Working in tandem with MetaMorph for Olympus software, ZDC2 Zero Drift uses an intermediate lens to focus to the desired z-position (depth) in the sample, automatically maintaining focus for seconds, hours, days or weeks. Using its automated continuous mode, users can easily retain precise focus even after reagents are added.

The IX81-ZDC2 Zero Drift provides crisp, sharp, bright images under time-lapse conditions. It can be used with a broad range of objectives including two key high-transmission Olympus TIRF lenses – the APON 60x, 1.49 NA and the UAPON 100x 1.49 NA objectives. ZDC2 Zero Drift also is an excellent choice for keeping focus during multi-modal calcium experiments that employ both TIRF and Fura-2. In conjunction with the Olympus cell^TIRF illuminator, the system allows simultaneous, high-speed multi-angle TIRF imaging.

The autofocus system is integrated into the Olympus IX81 microscope stand, known for its rigidity, stability and reliability. The small footprint of the IX81 houses a very efficient light path, and ZDC2 Zero Drift does not require the use of a second control pad or other accessories that can clutter the lab bench.

The ZDC2 Zero Drift tales advantage of the specimen-coverslip relationship. While the distance between the objective and coverslip can be affected by temperature, gravity, immersion media viscosity and other factors, the distance between the coverslip and an attached cell is much more stable. ZDC2 Zero Drift locates the specimen-coverslip interface very reliably and is able to return to the defined focus position with great accuracy, even if the objective-to-coverslip distance changes. Further, the system uses an autofocus routine that is significantly faster than conventional software-based algorithms and is unaffected by changes in morphology, contrast or fluorescence intensity of the cell. The laser can be turned off during periods when image acquisition is not occurring. In addition to TIRF, the autofocus system works well with high-throughput screening and other high-accuracy time-lapse studies of living cells in stage incubation systems.

More information here.

UNC-Olympus Research Imaging Center opens

The University of North Carolina (UNC) at Chapel Hill has opened the UNC-Olympus Research Imaging Center. The center is devoted to life science imaging and will provide researchers with advanced microscopes and camera equipment, software, consultation and expertise, in an environment intended to encourage scientific inquiry. The center is designed to stimulate collaboration among top life science research faculty members and will be available to guest researchers as well.

The imaging center has been endowed by Olympus America Inc., Center Valley, Pa., which is providing imaging systems featuring research microscopes, confocal instruments, digital imaging equipment, intravital imaging tools, incubation microscopes, software and substantial ongoing staffing and technical support.

It comprises nearly 2000 square feet of dedicated space and is codirected by Ken Jacobson, the Kenan Distinguished Professor of Cell and Developmental Biology, and James E. Bear, an Associate Professor and Early Career Scientist of the Howard Hughes Medical Institute. Both are affiliated with the Department of Cell and Developmental Biology at the UNC School of Medicine and the Lineberger Comprehensive Cancer Center. Researchers using the center work in cell biology, neuroscience, pharmacology and other specialties that contribute to the study of cancer, Alzheimer’s Disease and other conditions.

Microscope imaging software

Olympus has introduced cellSens microscope imaging software. The fully customizable software lets researchers move smoothly and quickly from image capture through processing, analysis and reporting. It also supports functions as deconvolution, cell counting, large area stitching, fluorescence unmixing and data sharing.

Developed by Olympus engineers specifically for Olympus microscope users, the software’s interface displays only the windows and tools the user needs at any given time. Researchers can customize the interface to streamline their individual workflows for more efficient imaging, processing, measurement, analysis and communication of data.

For researchers acquiring large amounts of data and working with colleagues in remote locations, the Database module provides a fully customizable SQL Server Express-based database that can be used locally or across global networks. The Olympus NetCam module offers live viewing over the Internet to further enhance collaboration. Researchers can exchange images and view data offline using cellSens Viewer software, a free download.

The system has a newly designed, lightning-fast constrained iterative (CI) deconvolution module that helps improve image resolution, sharpness and contrast. It delivers images of superior quality using a proprietary deconvolution algorithm. Researchers can further explore the resulting image with advanced 3D visualization via the software’s Voxel-Viewer feature.

cellSens Dimension allows options such as 5D-multidimensional acquisition for multi-wavelength, Z-stack and time-lapse experiments; an X-Y stage control module designed for multi-point acquisition and large area montaging; and comprehensive object measurement and classification tools. cellSens Standard meets the need for basic image acquisition and analysis with streamlined operation. cellSens Entry is designed for those who do not require the most advanced capabilities.

More information at www.olympusamerica.com/cellSens.

Three new upright microscopes for clinical/research laboratories

Olympus has unveiled its BX3 line of upright clinical and research microscopes with new ergonomic and imaging features that provide comfort, ease of use and accuracy. The line succeeds the Olympus BX2 microscopes and includes the BX43 System Microscope for clinical laboratory applications, the BX46 Clinical Microscope with ergonomic design and fast observation, and the BX53 System Microscope for research/clinical applications. All three systems employ the company’s proprietary UIS2 optics, which deliver ultra-sharp, bright images and are manufactured from lead-free glass.

The microscopes allow users to record and share microscope magnification and setting information automatically for comparing, measuring and scaling images. An exposure button lets researchers capture digital images without taking their hands off the microscope.

The BX43 and BX46 are designed for efficiency and comfort in clinical applications. They feature a bright LED lamp with halogen-like color fidelity that uses less energy and lasts approximately 20,000 hours. A Light Intensity Manager eliminates the need to make manual adjustments when changing magnifications. Users can select either left- or right-handed microscope operation. New to both instruments is an optional tilting, telescoping and lifting observation tube, which allows users to adjust the height, front-to-back position and tilt angle of the eyepieces independently. The BX46 features a stage height just three inches above the tabletop, which reduces fatigue, and a fixed stage that provides stability and accuracy in specimen positioning.

The BX53 research/clinical system offers new fluorescence optics and filters, including improved hard-coating technology and a unique fly’s eye array that delivers higher-quality images by providing more even illumination. It offers a unique motion sensor that detects when the user steps away from the instrument, automatically turning off the lamp after approximately 30 minutes, thus saving energy and providing longer lamp life. Both the BX43 and BX53 offer an optional new condenser that accommodates magnifications from 2x to 100x without requiring a swing-top lens.

More information at www.olympusamerica.com/BX3.

Olympus names distributor for industrial microscopes

Olympus America Inc. has named Leeds Precision Instruments, Inc., as the distributor for Olympus Industrial Microscope products in an expanded region to include Arizona, New Mexico, Colorado, Montana, Utah, Wyoming and eastern Idaho. The company will continue to represent Olympus in Minnesota, Wisconsin, North Dakota, South Dakota, Iowa, the Upper Peninsula of Michigan, and Texas.

According to Olympus, Leeds provides excellent service its customers in the biological and industrial instrument arenas and its custom design capability, systems integration and commitment to service and training make it a respected resource for industrial users and a valued partner to Olympus.

Three new TIRF microscopy objectives

Olympus has introduced three new high-performance TIRF objectives. The 150x ultra-magnification objective offers a numerical aperture (NA) of 1.45 for optimal magnification, resolution, light gathering ability and imaging performance, and the 60x and 100x oil immersion objectives have NAs of 1.49.

The 150x UAPON objective is optimized for single molecule TIRF applications. It delivers the high magnification and low background noise necessary for visualizing challenging specimens. The objective delivers crisp images from 340nm ultraviolet (UV) to near-infrared wavelengths and comes with a correction collar to help compensate for aberrations caused by coverglass thickness or variations in immersion media temperatures.

The 100x UAPON objective also is newly enhanced with a correction collar, and has been updated to include near-UV performance. The 60x APON provides the brightest high-resolution TIRF images available, thanks to its improved point spread function.

More info at http://www.olympusamerica.com/tirf_objectives.

Omnyx licenses Olympus digital pathology patents

Olympus America Inc. has signed a nonexclusive worldwide licensing agreement with Omnyx, LLC, a joint venture of GE Healthcare and the University of Pittsburgh Medical Center. The agreement will give Omnyx access to a portfolio of Olympus America virtual microscopy and digital pathology patents, which will aid the development of future imaging and data handling technologies for the review and management of millions of biopsy slides and other pathology specimens now handled using glass slides and traditional optical microscopes.

The patents cover software and technology related to creating, storing and delivering virtual microscopy images. Virtual microscope slides enable biopsies and other pathology images to be viewed without handling traditional glass slides, and allow doctors to share high-resolution digital microscope images over the Internet for remote pathology consultation. Virtual microscope slide technology also has the potential to aid hospitals in moving to comprehensive patient electronic medical records.

Fluorescent reporter allows imaging of single cells infected with hepatitis C

Hepatitis C virus (HCV) infects 2 to 3 percent of the world population. The recent development of methods to culture the virus may lead to antiviral therapies, but better imaging methods are needed to understand the infection process. In the February issue of Nature Biotechnology researchers at Rockefeller University, MIT and other institutions report on a cell-based fluorescent reporter that allows imaging of live or fixed individual HCV-infected cells.

They constructed the reporter by fusing a fluorescent protein--either EGFP, mCherry, or Tag RFP--to the C-terminal region of a known substrate of the HCV NS3-4A protease. They were able to use this reporter to distinguish between infected and uninfected cells and to image previously unseen events such as viral propagation and host response. The researchers used a Nikon Eclipse TE300 for wide-field fluorescence imaging, a Zeiss inverted Axiovert 200 laser scanning confocal microscope for imaging fixed samples, the Axiovert 200 with a Perkin-Elmer spinning-disk confocal head for imaging live samples, and a Olympus IX71 inverted microscope for time-lapse imaging.

The reporter system doesn’t require genetic modification of the viral genome and worked for all the HCV genomes they tested, which gives it potential for use in identifying new infectious isolates directly from patient samples, according to the researchers. They were also able to combine the HCV reporter with a fluorescent marker of cellular stress to correlate viral and host events.

Research Paper:
Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system, Nature Biotechnology 28, 167 - 171 (2010) 
doi:10.1038/nbt.1604

Microscope illuminator for multicolor TIRF imaging

Olympus has released the cell^TIRF illuminator. The system has four motorized laser channels for simultaneous image capture and allows instant setting and confirmation of the precise TIRF angle. Each of the four individually controlled laser inputs is optimally focused and the angle of each can be adjusted so that all wavelengths have the same penetration depth. Calculated penetration depths can be preset for all four lasers and used with a single mouse click; the system will automatically adjust the angle of each laser to simultaneously capture TIRF from all four channels. In addition, one laser line can be adjusted for FRAP experiments, and users can easily switch to widefield view and then reestablish TIRF imaging in less than 500 ms.

More information here.

Use one laser for two multiphoton microscopes

At the Society for Neuroscience conference last week, Olympus introduced new accessories for two-photon confocal microscopy. The new Laser Sharing System, Dual-Port SIM Scanner, and Multi-Point SIM scanner software enhance the capabilities of the company’s FluoView FV1000-MPE multiphoton system.

The Laser Sharing System lets researchers use a single Spectra-Physics Mai Tai DeepSee laser system to perform imaging experiments on two separate Olympus multiphoton systems. It optically redirects laser light to the second multiphoton system, providing flexibility and saving money for those who want to install multiple two-photon instruments. The microscopes can be used simultaneously with the laser if using the same wavelength of light.

The Dual-Port SIM (Simultaneous) Scanner is for experimental protocols requiring photobleaching with both visible and infrared (IR) light. With the scanner, the user can use both wavelengths without changing any optics or fibers, eliminating laser alignment issues, saving time, and cutting down on hassles that can interfere with imaging.

The SIM scanner software is useful for neuronal spine research in that it lets the user rapidly stimulate multi-point areas. The software has a dedicated neuroscience application and enables control of the scanner, laser, and dataset for stimulation applications used in uncaging or channel rhodopsin experiments. The software visualizes the signal not only from the confocal photomultiplier tube (PMT) but also from electrophysiology patch-clamp equipment through a new interface unit.

More information here.

Remote viewing of scanned microscopy images

Microscopy slide scanners are useful for automating image acquisition and for archiving slides to examine more closely at a later time. Now there’s a new option for slide scanning, the Olympus VS110 virtual slide scanning system. The system, which is now available in the US, can scan from one to 100 slides. Remote users can view and navigate high-resolution images of entire slides or areas of slides on a network or web browser, and they can add linked annotations, markers, dictation, and files.

The system comes standard with Olympus Plan Apo 2x, 10x, 20x and 40x objectives, and optional 60x and 100x Plan Apo oil objectives are available. Multiple Z focal planes can be captured and displayed using the Virtual-Z™ feature. The system uses a Peltier-cooled 1376 x 1032 pixel camera with low background noise, fast frame rates, high sensitivity, excellent signal-to-noise ratio, and a broad dynamic range. In addition to single-specimen brightfield microscopy imaging, the system can handle tissue microarrays (TMAs).

Three models are available:
• VS110-1: Each slide is loaded manually and a virtual file is created automatically based on the user’s preferences
• VS110-5: Automated scanning of up to five slides.
• VS110-L: Has a 100-slide robotic loader for automated scanning and slides can be selected sequentially, at random, or via the software.

Find more information here.

Five resources on LED microscopy illumination

1. Tutorial on Zeiss product: LED illumination system for widefield fluorescence microscopy

2. Leica product: LED fluorescence light source. 

3. Thorlabs LED products:

Collimated LED Light Source

Modulated LED sources for FLIM

4. Article covering CoolLED product (available from Olympus): "LEDs for fluorescence microscopy" 

5. Research paper: "A new type of microscope illumination and its use in microbiology".

New CMOS camera and workflow software

Capture color
If you’re looking for versatile yet affordable color camera, you might try the  Olympus SC30 microscopy camera that was recently introduced in Europe. Suitable for material and life science applications, it has a native resolution of 2048 x 1532 pixels, uses a 3.3 megapixel CMOS chip, features exposure times that can be adjusted from 57 µs to 1.75 s, and has binning modes of 2x, 3x, and 4x. It can be used for live cell imaging, standard bright field applications, and for digital documentation. With 4x binning, it can capture 49 fps at resolution of 508 x 384 pixels. More info here. 

Get more done
Macnification digital electron microscopy shareware for the Mac could increase your productivity. It helps users organize, find, annotate, analyze, adjust, compare, and publish microscopic images. All major image file formats can be imported, and measurement results can be exported to spreadsheet applications. Requires Mac OS X 10.5 or later. More info here. 

Less embryo phototoxicity with spinning disk/EMCCD microscopy setup

Electron multiplying (EM) CCD cameras have helped spinning disk confocal microscopy find more use because the cameras are sensitive enough to detect the low levels of light produced by the microscopy method. For living specimens, this type of microscopy brings the benefits of reducing phototoxicity during the repeated exposures used to acquire time-lapse images or z-axis slices.

Researchers at RIKEN-Kobe in Japan recently used this win-win technology pairing to image mouse embryos. They published a paper in the Journal of Reproduction and Development describing how their methods decreased phototoxicity so much that preimplantation mouse embryos could undergo long-term time-lapse imaging, be implanted, and then survive full-term.

They used an Olympus inverted microscope with a Nipkow disk confocal module and an Andor EMCCD camera. A CVI Melles Griot 70 mW agron-krypton laser provided the confocal light source. The mouse embryos were injected with a mixture of mRNAs encoding for enhanced GFP coupled to alpha-tublin and monomeric RFP fused to histone H2B. At specific time points, the researchers acquired 51 images in the z-axis with 488 and 561 nm excitation. Imaging took place for 70 hours.

Although the setup lessened light exposure, the researchers found that the interval between observations was another important factor -- an interval of 7.5 min. increased embryo viability greatly over 3.75 minutes. They also found that continuous light exposure was worse than repeated intermittent excitation, even when the total exposure was equal.

This microscopy method could aid study of development and assistive reproductive techniques in mammals. For example, it could help reveal why some assistive reproductive techniques (such as in vitro fertilization) work better than others, and it might be used to identify healthy embryos prior to implantation.

In the paper, the researchers pointed out that the mechanisms behind phototoxicity are still not completely understood and that their findings regarding phototoxicity imply that embryos may be able to neutralize toxicity. To find out more about this topic, I am going to compile some of the latest research on photoxicity.

Are you performing research in the area of phototoxicity, or do you know of a good resource?

Image: These time-lapse images show spindle (green) and nuclear (red) dynamics during preimplantation embryo development. Courtesy of Kazuo Yamagata, RIKEN-Kobe.

Note: If you want to know more about EMCCDs, Photometrics is holding webinar covering this topic on Friday April 3: http://tinyurl.com/cwarev.

Olympus buys microscope distributor business

I have observed some microscope companies moving slowly away from using regional distributors to sell their products, opting instead to work directly with their customers. In line with that trend, Olympus America Inc. today announced an agreement with Optical Analysis Corp. -- a company based in Nashua, NH that distributes and resells scientific instrumentation and systems. As of April 1, Olympus will have acquired the company's microscope, imaging and image analysis business. This means that Olympus will begin selling microscopes directly in Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine, Indiana and parts of Illinois and Michigan, and it will work directly with current Optical Analysis customers. Olympus uses direct and dealer sales, depending on the region.

While I know many distributors have great relationships with their customers and with microscope companies, if I were going to spend significant money on a microscope system I would want to work directly with the manufacturer. The complexity of today's microscopes, software, and accessories makes it difficult for anyone to know it all. This complexity added to tight budgets mean that customers want to be fully informed. They want to be sure they are getting the very best setup for their needs and for their money. A microscope company can have employees that specialize in certain types of microscopes or in specific methods, whereas, distributors may not have the number of employees needed to develop this type of expertise. Plus, the microscope manufacturer can make the decision of when a customer's interest warrants a visit from a more advanced expert - whether it is a matter of money or an innovative application.

What are your experiences with distributors vs. working directly with a microscope company?

News Source: Olympus Press Release