C. elegans on a chip

Rather than studying C. elegans one at a time, a device developed by researchers at Harvard University and Tulane University allows an array of individual worms to be observed over their entire lifetime. Each worm gets its own chamber, with food delivered and waste removed via microfluidic channels. An optional wedge-shaped channel in each chamber can immobilize the worms for high-magnification imaging (at least 400 X, the researchers say) or laser microsurgery. The device should be useful for observing long-term behaviors, phenotypes that may change with age or in response to a stimuli, and variation among a population.

Research paper: Lifespan-on-a-chip: microfluidic chambers for performing lifelong observation of C. elegans. S. Elizabeth Hulme, Sergey S. Shevkoplyas, Alison P. McGuigan, Javier Apfeld, Walter Fontana and George M. Whitesides. Lab Chip, 2010, 10, 589–597 DOI: 10.1039/b919265d

Polarizer added to handheld microscope

I mentioned the Digital Mighty Scope in my earlier post, Five digital microscopes under $300. Now, the second generation of the handheld microscope is being released from Aven Inc. It features a contrast-enhancing polarizer for viewing and taking digital close-ups of polished metal, silicon chips, ceramic, glass, and other shiny objects. In addition to industrial quality control, polarized light microscopy also is ideal for examining minerals, polymers and biological materials.

The microscope is like a mini-camera that zooms, providing polarized light views of electronic components, manufacturing parts, circuit boards, crystals and other items. Users can detect hairline cracks or other microscopic defects, as well as identify specimens reliably.

The microscope has magnifications adjustable from 10 to 200X. A brightness wheel allows fingertip control of polarized illumination from six white LEDs. Active pixel sensors provide sharp images and accurate color reproduction from the 1.3-megapixel camera. A USB connection to any laptop or desktop computer lets users edit images, share them and add them to presentations or publications. Microsoft-compatible software is included, with an upgraded version available as an option to provide a broader range of image annotation, measurement and manipulation.

The company will demonstrate its advanced Digital Mighty Scope at Pittcon 2010 in Orlando, Fla., next month.

More information at www.aveninc.com.

Microscopy hits the big screen

I love to hear about anything that might get people excited about science, especially if it involves microscopy. I can’t wait to see PassmoreLab’s new 3-D movie called MicroWorlds. The live-action educational science film explores the life that goes on, unseen, all around. The film examines the life of earthworms, ladybugs, butterflies and garden snails, portraying their everyday actions and the vital role they play on our planet.

The film was shot in California with a custom 3D microscopy setup designed for the film. High-precision stages, macrolighting, and a year of intense shooting produced the never before seen imagery. The film mixes stereoscopic microscopy, time-lapse imaging, and some serious bug wrangling. Everything was shot at high def and with a broad dynamic range.

Seeing a ladybug 30 feet tall on screen gives the audience a different perspective and a great amount of detail on organisms that might seem ordinary. PassmoreLab also created a complete teacher's guide full of trivia, games and mind-benders germane to the film. The companion piece is available for middle-schoolers that want to dig a little deeper into the science of the film after seeing it.

MicroWorlds will be available in 3D Digital in March.

For more info at www.passmorelab.com/microworlds.

Power measurement for fluorescence microscopy

The X-Cite XR2100 Power Meter and the XP750 Objective Plane Power Sensor for fluorescence microscopy are new from EXFO Electro-Optical Engineering Inc.’s Life Sciences and Industrial Division. The products allow microscopists to measure the optical power at the specimen to ensure consistent and repeatable illumination throughout their experiments.

The X-Cite XR2100 power meter (pictured) has a control keypad interface and can store power measurements or export them to a computer, allowing power data files to be kept with imaging data. The Objective Plane Power Sensor fits on the microscope stage and can measure output from an X-Cite illuminator or any other epifluorescence light source, including HBO/mercury, metal halide or xenon lamps, lasers and LEDs. It has is sensitive to powers from 5 µW to 500 mW at 320 nm to 750 nm.

More information here.

Look for me at the Society of Neuroscience

On Sunday and Monday I will be blogging about new microscopy products and research at the Society of Neuroscience for Microscopy and Analysis. Look for posts at www.microscopy-analysis.com, and I will also have links to the posts here. Hopefully, I'll get some Twittering in as well.

I will be working with the M&A editor on which companies and research I cover, but if you would to be put in for consideration and have an exciting new microscopy product or research please e-mail me at microscopynews@aol.com.

See you in Chicago!

Vote for your favorite microscopy images in the Small World People’s Choice Award

Although the official judging for this year’s Nikon Small World Photomicrography competition took place earlier this year, you can still have a say in the People’s Choice Award by voting on your favorite images.

Have your say by rating images on a scale of 1 to 5 stars (5 being the best). Nikon asks that you rate each image only once. After voting closes on Oct. 2 at 5 pm EST the images will be ranked by their average score to determine the winner of the 2009 Small World People's Choice award. You can see how your picks did in the judged competition once those winners are announced on October 8.

Vote at www.nikonsmallworld.com/vote.

Computer mouse benefits from dark field microscopy technology

Today’s optical and laser computer mice offer accurate tracking but have trouble handling shiny surfaces or glass. With more people using laptops, they are more likely to use their computer on shiny surface such as a dining room table, a kitchen counter, or a table at the local coffee shop. Logitech set out to develop a mouse that could handle any surface without requiring a mouse pad. The company considered Doppler radar, UV imaging and interferometry techniques but decided that the principles of darkfield microscopy were the best solution.

Standard optical and laser mice use a light source to illuminate the surface, and a lens captures the scattered light. An image sensor with an onboard processor processes the generated image, using minute differences between images to determine the direction and speed of motion. Since glass and shiny surfaces may have very few irregularities, it can be hard for the sensor to identify reference points for measuring motion.

Dark field illumination can help reveal microscopic details of a shiny tracking surface because it contrasts small particles such as dust or scratches against a black background. The Logitech implementation of the technology uses two lasers to more effectively collect details from a shiny surface and switches to only one laser when used on a normal surface. The Logitech Darkfield Laser Tracking technology is used in the company’s Anywhere Mouse MX and Performance Mouse MX, which were introduced last month.

Read more about this technology here and the mice here.

New microscope for life sciences and materials is ideal for multiple users

Carl Zeiss has launched the Axio Imager 2, a microscope for biomedical research and materials applications. The microscope comes in custom configurations with ten stand versions. All of the stands feature a light manager separately stores and reproduces the illumination intensity for each magnification. The ability to store system parameters for up to ten users makes the microscope system ideal for multiple users.

For live cell imaging, the new optical design of the transmitted light beam path and of the condensers allows homogeneous illumination at low magnifications and increases the working distance. The microscope’s ability to automatically switch between reflected and transmitted light and to generate mixed light are useful for growing research field of bionics. In addition, sample-induced artifacts are prevented becuase the motorized modulator turret for transmitted light DIC makes it possible to set differential interference contrast reproducibly and, in combination with fluorescence image acquisition, to remove the DIC prism automatically from the light path. 

Find more information here.

Better position control with new deformable mirror controller

When performing microscopy, optical aberrations can arise from a mismatch of the refractive index of the immersion medium and the sample or from refractive index variations within the sample. Such aberrations can lessen the image quality. Adaptive optics systems can correct for these aberrations. Such a system measures distortions in a wave front and compensates for them with a spatial phase modulator such as a deformable mirror.

Boston Micromachines Corp. makes deformable mirror systems for use in adaptive optics, and now the company has announced a new high speed, high precision controller for its Mini-DM (deformable mirror). The controller comes in a package five times smaller than the previous version, and it achieves position control with14 bit resolution at a >8 kHz frame rate.

The Mini-DM can be used for laser beam shaping in proof-of-concept experiments and in microscopes and ophthalmic instruments. The wavefront control device consists of a mirror membrane supported by an underlying actuator array. Each actuator can be individually deflected by electrostatic actuation to achieve the desired pattern of deformation.

Inaugural Microscopy Society of America fellow

Yimei Zhu, a scientist at the U.S. Department of Energy’s Brookhaven National Laboratory, has been elected the inaugural Fellow of the Microscopy Society of America. The designation recognizes senior distinguished members of the society who have made significant contributions to the advancement of the science and practice of microscopy.

Zhu will formally receive the award at the Microscopy and Microanalysis conference, the society’s annual meeting held in Richmond, Virginia later this month. His citation reads: “For outstanding and innovative development and implementation of advanced electron microscopy techniques including quantitative diffraction, imaging, spectroscopy, and phase retrieval methods in understanding superconducting, ferromagnetic, and strongly correlated materials.”

Zhu’s research has included the study of the structure and properties of materials such as thermoelectirics that can convert heat to electricity, superconductors that can conduct electricity with no energy loss, and materials that can be used in magneto-electronic devices at nano-scale dimensions for applications ranging from digital communication to data storage.

Zhu earned a B.S. in materials physics from JiaoTong University, Shanghai, in 1982, and was one of the first few students selected in China to pursue graduate study abroad after the country opened its doors to the West. He received his M.S. and Ph.D., also in materials physics, from Nagoya University, Japan. He is now a senior scientist at Brookhaven and an adjunct professor at Columbia University and Stony Brook University.

An automatic supply of water for water-immersion microscopy

Water immersion objectives are important for abberation-free focusing into live cell samples. However, the fact that water evaporates creates a challenge for long-term experiments. The new Water Immersion Micro Dispenser from Leica Microsystems can help over come this challenge. It can be retrofitted to water immersion objectives, and it automatically pumps water from a small water reservoir magnetically attached to the center of the objective nosepiece. 

The correction ring stays accessible and the full free working distance of the water objective is maintained. The design of the water cap keeps the water droplet in place even when the stage is moved. The water is dispensed at the right temperature and thus does not require heating. A protective collar around the objective prevents any water from getting into the microscope. The Water Immersion Micro Dispenser is designed for the Leica DMI6000 B inverted microscope, which is a component of confocal as well as high-end widefield systems.

New CMOS technology for scientific applications

Andor Technology of Belfast, Northern Ireland, Fairchild Imaging of Milpitas, California, USA, and PCO AG of Kelheim, Germany have been working together on a brand new CMOS technology. They introduced the technology by presenting a white paper on the technology at the Laser World of Photonics in Munich on June 16.

According to the companies, the new technology--called scientific CMOS (sCMOS)--will benefit many microscopy applications such as live-cell, super-resolution, and spinning-disk confocal microscopy as well as TIRF, FRAP, FRET, and single molecule detection.

The technology looks to be a significant advancement for biological imaging because it overcomes some of the drawbacks of many sensor technologies, including interline CCDs and electron multiplying (EM) CCDs, which are often used in demanding microscopy applications. sCMOS can simultaneously provide low noise, rapid frame rates, wide dynamic range, high quantum efficiency (QE), high resolution, and a large field of view. 

Here are the numbers for the first sCMOS sensor:

• Sensor format: 5.5 megapixels (2560(h) x 2160(v))
  
• Read noise: <> 16,000:1 (@ 30 frames/s)
  
• QEmax.: 60%
  
• Read out modes: Rolling and Global shutter (user selectable)
  

The white paper provides data and images comparing the sCMOS technology with EM and Interline CCDs. All three companies plan to have cameras using the new technology in 2010, some as early as first quarter.

Get more information on the sensor technology and the white paper at www.scmos.com.

More on this development in the blog post: Is the sCMOS too good to be true? 

Microscopy events June-Sept

Andor Webinar
June 25
This 60 minute interactive webinar will be delivered by Dr. Mark Browne, Andor’s Director of Systems. It will focus on the company’s new Clara CCD camera, the UVP-350i laser platform for pulsed UV uncaging and ablation, and Differential Spinning Disk technology for white light confocal imaging.
More information here.

Principles of Fluorescence Techniques
June 29 - July 2, Genova, Italy
Sept 14-17, Madrid, Spain
Theoretical lectures will be complemented by the chance to use steady state and lifetime fluorescence instruments and confocal microscopes for FLIM and FRET applications. Topics will include:
• Basic Definitions and Principles of Fluorescence
• Fluorescence Polarization
• Time-resolved Fluorescence
• Instrumentation
• Data Manipulation and Data Analysis
• Non-Linear Microscopy Including SHG
• GFP Fluorescence and Photoactivation
• Confocal and Multiphoton Fluorescence Microscopy
• FCS, Fluorescence Correlation Spectroscopy
• FLIM, Fluorescence Lifetime Imaging
• Single Molecule Imaging
• Image Processing and Deconvolution Approaches
More information on Genova course here.
More information on Madrid course here.

Taiwan Bioworkshop
National Taiwan University (NTU)
July 30-31
In conjunction with the NTU National Health Institute in Taiwan, Asylum Research presents the first Taiwan Bioworkshop. The free workshop will feature AFM lectures and a hands-on workshop. Topics include:
• Principles of AFM
• High resolution molecular imaging
• Cell imaging
• Force measurements
• Combined AFM and optical imaging
More information here.

These events are now added to the microscopy news google calendar 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.

Microscopy images reveal how B cells are activated

Researchers at Sydney's Garvan Institute of Medical Research and the University of California San Francisco have captured microscopy images that reveal some important new details of how the immune system works.

The researchers were interested in knowing what drives the immune system's B cell activation and where it occurs. B cells produce antibodies in response to a specific invaders’ antigens. These antibodies help fight the invader at that time as well as in the future. Scientists have not understood how these B cells get exposed to the invader’s antigens if macrophages and dendritic cells are constantly destroying the invaders.

The researchers studied these immune interactions in a living mouse’s lymph nodes--where invaders are brought to be destroyed by macrophages and dendritic cells. Intravital and multiphoton microscopy images revealed highly specialized 'subcapsular sinus (SCS) macrophages' embedded in the lining of the lymph nodes’ sinus. The images showed the heads of these macrophages capturing the antigen on one side of the lining and their tails delivering it to B cells on the other side of the lining. In other words, the intact antigen passes through the subcapsular sinus almost like it is on a conveyer belt. 

This finding helps to clarify other groups’ observations of unusual macrophages in the subcapsular sinus and B cells residing nearby, and it clarifies how and where the B cells become activated. View videos of findings are here.

Research paper: Tri Giang Phan, Jesse A Green, Elizabeth E Gray, Ying Xu & Jason G Cyster, Nature Immunology, Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation. Published online: June 7, 2009, doi:10.1038/ni.1745.

Image courtesy of the U.S. National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program.

Folio photomicroscopy contest

Get your best microscopy images ready. Entries are now being accepted for a photomicroscopy contest sponsored by Folio Bioscience and Cell Press. The submissions deadline is September 1, 2009, and the images will be judged on technical quality, clarity, and composition. The grand prize winner gets a Nikon D300 camera (estimated value: $1,800 USD). Get all the rules and info on how to enter here. 

Fluorophore blinking harnessed for super-resolution fluorescence microscopy

Most fluorophores naturally switch between fluorescent and dark states. This blinking can be problematic for some types of imaging, but researchers at Ludwig-Maximilians-Universität in Munich, Germany have harnessed the blinking to accomplish super-resolution fluorescence microscopy.

Other researchers have used photoswitchable fluorophores for high-resolution imaging, but the technique published in a recent issue of PNAS overcomes some of the limitations of previous methods by working in the presence of oxygen and using ordinary fluorophores. The Ludwig-Maximilians researchers achieved precise control of oxazine dye fluorescence by adding or removing reductant or oxidant, which switched the flourophore between stable fluorescent and nonfluorescent (dark) states. Depending on the switching rate, they achieved 400 and 3,000 switching cycles before irreversible photodestruction.

Subdiffraction resolution microscopy can be accomplished if most fluorophores in a diffraction-limited area are in the dark state. A sensitive camera resolves the location of any remaining fluorescing fluorophores. Using their method to control the dark state of fluorophores, the researchers imaged actin filament and actin filament bundles in fixed cells. The resulting images show many details not resolvable in the total internal reflection fluorescence images of the same area. Such fine control of fluorophore states could also be useful for activating molecular switches for nanotechnology devices.

Research paper:
Jan Vogelsang, Thorben Cordes, Carsten Forthmann, Christian Steinhauer, and Philip Tinnefeld, Controlling the fluorescence of ordinary oxazine dyes for single-molecule switching and superresolution microscopy, PNAS 2009

Subnanometer positioning for microscopy

The new PI nano series nanopositioning stages can be used for scanning microscopy, single molecule microscopy, 3D imaging, and autofocusing. They have a 20 mm (0.8 in.) profile, a large aperture and deliver subnanometer resolution in 2 and 3 axes. The included piezo controller has a 24-bit USB port, Ethernet, RS-232, and an analog interface, and it supports all major image acquisition software. The piezo stage can be used with the optional M-545 manual XY microscope stage, which is available in different versions for Olympus, Nikon, Zeiss and Leica microscopes.

For highly stable, closed loop operation, piezoresistive sensors are applied directly to the moving structure and precisely measure the displacement of the stage platform. The very high sensitivity of these sensors provides optimum position stability and responsiveness as well as sub-nanometer resolution. The proprietary servo controller significantly improves the motion linearity compared to conventional piezoresistive sensor controllers.

Image shows the piezo controller (background) and the optional manual XY microscope stage with the PInano XYZ piezo stage on top (foreground). 

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".

Two-photon microscopy with 113.5-nm resolution

Two-photon microscopy is very useful for imaging living tissues, but the method’s restricted excitation volume typically comes with the trade-offs of lower spatial resolution (especially in the axial direction) and slower imaging than one-photon imaging. Multi-focal multiphoton microscopy–which uses multiple focal spots excitation instead of a single spot–looks promising for overcoming these drawbacks.

Researchers at the Chinese Academy of Science in Shanghai and Sun Yat-sen University in Guangzhou, China have reported their work to improve on the multi-focal technique in the latest issue of the Journal of Microscopy. They produced high-speed two-color two-photon microscopy with improved transverse and axial resolutions by using a 3-D optical lattice made by multi-beam interference and two excitation wavelengths. With 400 and 800 nm excitation they were able to produce 113.5 nm resolution in the transverse and axial directions while imaging faster than is possible with traditional two-photon microscopes.

Research paper: Journal of Microscopy, Two-colour two-photon confocal microscopy with isotropic three-dimensional resolution and parallel excitation, Volume 234 Issue 2, Pages 205 – 210.