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Nakamura Gives Some Credit to Maruska for Blue LED Invention

Shuji Nakamura held a teleconference with the media yesterday to discuss his invention of the blue LED—for which he was recently awarded the 2014 Nobel Prize in Physics—and how it led him to found the LED company Soraa. Nakamura worked at Nichia Chemicals in Tokushima in the 1980s and 90s, where he developed a commercially viable gallium nitride-based blue LED.

During the Q&A, Nakamura—who shares the Nobel prize with Isamu Akasaki and Hiroshi Amano—told reporters he believed recognition for the blue LED should also extend to Herbert Paul Maruska, a researcher at RCA who created a functional blue LED prototype in 1972. Nakamura said he did not think his or Akasaki and Amano’s work would have been possible without Maruska’s contributions many years prior.

Nakamura also mentioned his hope that within five years, laser diodes would finally be commercially available, especially for use in car headlights. For several years, Soraa has worked on developing headlights powered by a blue-laser diode, shown to be 1000 times as bright as an LED while using two-thirds the energy.

Read about the history behind Maruska’s blue-LED work at RCA, and also check out our October 2013 feature on laser headlights.

Photo: Herb Maruska

Printed Dots Detect Ebola (and More) Without a Lab

In their new paper in the journal Cell, Keith Pardee, James J. Collins and colleagues from Collins’ lab at Harvard’s Wyss Institute for Biological Inspired Engineering talk about networks, printing circuits, programming, and even orthogonality.

They’re not talking about electronics, though. They’re describing how they developed “paper-based synthetic gene networks” into a practical, and potentially revolutionary, diagnostic tool for detecting a wide range of biomolecular targets such as glucose and viruses.

It took them less than a day to produce a slip of paper that can detect the Ebola virus. Armed only with that slip and smartphone camera, a healthcare worker in the field could know within two hours—and sometimes in as little as 20 minutes—whether a patient is infected or not. And the doctor, nurse, or volunteer could do this without advanced skills, extensive sample preparation, expensive reagents, laboratory instruments, or even refrigeration.

“Our paper-based system could not only make tools currently only available in laboratory readily fieldable, but also improve the development of new tools and the accessibility of these molecular tools to educational programs for the next generation of practitioners,” wrote Collins.

To produce a synthetic gene network, selected chunks of DNA, RNA, proteins, organelles (including, importantly, the ribosomes that read messenger RNA, or mRNA, and translate it into proteins), and other biomolecules are freed from their cellular casings and isolated into a complete but non-living physiological pathway.

The Wyss researchers engineered their synthetic network, painted the stew onto paper (or cloth, or any other porous medium), and freeze-dried it into an inert dot. Add water and a bit of a triggering analyte—DNA from a suspicious virus, say—and the synthetic network goes to work, activating a cascade of reactions that causes the printed dot to change color. The approach could be used for detecting not just viruses, but a staggering variety of other targets.

A “toehold hairpin RNA” sensor is a key to the process. If a single strand of RNA includes complementary sequences at separated stretches along its length, it can fold back upon itself to form a hairpin. The Wyss researchers engineer an RNA sequence so that it includes: a stretch of detector RNA that will bind to messenger RNA produced by the target (a transcript Ebola virus produces to build coat proteins for new viruses, for example); a ribosome binding site sequence, which will prompt the ribosome to grab the molecule and start reading its instructions to make protein; a “closure” sequence that binds to the detector RNA, hiding the ribosome binding site in the loop of the hairpin; and mRNA instructions for an enzyme (such as beta-galactosidase) that will alter the structure of a reporter molecule (such as a yellow form of galactose) to change its color (say, to a purple). [See the video here.]

Mechanism of the Toehold Switch. Wyss Institute Postdoctoral Fellow Alex Green, Ph.D., the lead author of "Toehold Switches: De–Novo–Designed Regulators of Gene Expression," narrates a step–by–step animation of the mechanism of the synthetic toehold switch gene regulator. (Wyss Institute via Vimeo)

The design leaves the toehold, a short strip of detector RNA, dangling free at the bottom of the hairpin. The target RNA latches onto the toehold and starts zipping up along the rest of the detector sequence—and unzipping the closure sequence. This opens up the ribosome binding site in the hairpin. The unfolded mRNA then passes through the ribosome, and the ribosome produces the enzyme. The enzyme reacts with the reporter and, voila, the color changes.

The color changes can be seen with the naked eye or digitally quantified. Conventional laboratory plate readers will certainly do the job. But along the way, the Wyss team also developed algorithms that allow most digital color cameras, including those available in cellphones, to quantify color changes in the gene-network dots.

Pardee, Collins, and their colleagues report that paper-based synthetic gene networks offer a number of advantages, including cost, speed, and rapid development, over conventional diagnostic approaches.

Cost. Paper-based diagnostics could cost as little as US $0.02 to $0.04 per sensor, they say. This is dramatically lower than the $0.45 to $1.40 for familiar antibody-based rapid diagnostics tests (RDTs) like home pregnancy and glucose kits, and the $1.50 to $4.00 cost of the reagents used in a PCR (polymerase chain reaction) DNA assay.

Speed. The paper-based synthetic gene network diagnostics the Harvard team produced are about as fast as antibody-based home tests, a little faster than PCR, and much faster than the bacterial and viral culture methods that have been a diagnostic mainstay. The Wyss group’s paper diagnostics produce detectable color changes in 20 to 40 minutes (or perhaps longer, depending on the assay and the concentration of the target molecule). Antibody-based RDTs show results in about 20 minutes. And PCR assays require at least 60 minutes…and a well-equipped laboratory.

Rapid Development. As an exercise, the Wyss researchers gave themselves a day to develop an assay capable of detecting the Ebola virus, and of distinguishing between its Sudan and Zaire strains. They produced 24 Ebola sensors in less than 12 hours.

“Taken together,” the Wyss researchers conclude, “and considering the projected cost, reaction time, ease of use, and no requirement for laboratory infrastructure, we envision paper-based synthetic gene networks significantly expanding the role of synthetic biology in the clinic, global health, industry, research, and education.”

Images: Wyss Institute/Harvard University

Cree Engineers a Cheaper LED Bulb by Losing the Heat Sink

Heat sinks have made LED bulbs the freaks of the lighting world. Metal collars and other heat sinks serve to draw away heat from LEDs to ensure long life, but they also give LED bulbs an unfamiliar, bulky look and add to their costs.

LED maker Cree on Tuesday is introducing a new consumer bulb that does away with the metal heat sink seen on most LED bulbs. The dimmable bulbs come with a lower cost, too: $7.97 for a 40-watt and 60-watt equivalent, down from $9.97 for a “soft white” version. The “daylight” version with whiter light costs $8.97.

The new design employs a few engineering tricks and the company's latest generation of high-power LEDs to reduce the cost, says Mike Watson vice president of strategy at Cree, which makes LEDs atop silicon carbide wafers.

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Neuroscience Gets Radical: How to Study Surfers' Brain Waves

When the energy drink company Red Bull flew a team of neuroscientists and elite surfers to a beach town in Mexico in late August, it was in hopes of answering a vexing question: How can you study the brain waves of surfers while they’re actually riding the waves? 

Some people might consider another question more pressing: Why would you want to? But Red Bull already had an answer for that one. The company wanted to know “what stoke looks like in the brain,” says Brandon Larson, a technologist on Red Bull’s R&D team. (You read that correctly. It’s stoke not stroke.) When a surfer is stoked, Larson says, that person is “in the zone,” and performing at peak potential. If scientists can find the biomarkers of stoke, maybe coaches can use the information to help surfers achieve that hallowed state of mind. 

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Feds Probe Cybersecurity Dangers in Medical Devices

When person’s survival is reliant upon medical implants and other devices with computer chips, the potential consequences of cybersecurity flaws can be deadly. The U.S. Department of Homeland Security is now looking into at least two dozen cases of possible cybersecurity flaws in medical devices ranging from artificial heart implants to hospital infusion pumps.

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See-Through Sensors for Better Brain Implants

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Brain scientists first discovered how to use light to remotely control genetically-modified brain cells about a decade agoa breakthrough that has enabled new scientific studies of depression, addiction and Parkinson’s disease. Now a new generation of transparent brain sensors could record brain cell responses without blocking the light’s access to the underlying brain tissue.

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Nobelist's New Microscope Captures Life in Action

In December Eric Betzig is expected to fly to Stockholm to receive his share of the 2014 Nobel Prize in Chemistry for expanding the frontiers of microscopy. It seems he just couldn’t leave those frontiers alone. 

In a tour de force paper in Science, Betzig and his collaborators have introduced a new method for imaging biological processes with unprecedented resolution in space and time.  Betzig and Bi-Chang Chen, Wesley R. Legant, and Kai Wang from his lab at the Howard Hughes Medical Institute’s Janelia Research Campus were joined by collaborators from 14 other groups around the world to come up with the new microscopy method.

The technique, called lattice light-sheet microscopy, generates extraordinarily sharp, 3-D images and videos of live organisms at scales ranging from single molecules to early-stage embryos. It builds on other methods Betzig has pioneered. 

One of those methods was something  the Nobel Prize committee mentioned in making their award, Betzig’s development of photoactivated localization microscopy (PALM). PALM lets researchers see objects smaller than the half-wavelength diffraction limit—by shining less light on the subject, rather than more.

The diffraction limit is the light microscopist’s nemesis. Violet light has the shortest wavelengths most humans can see, down to about 380 nanometers (though some people who have lost their corneas to cataract surgery can see into the ultraviolet, to perhaps 300 nanometers). Thus, objects smaller than about 200 nanometers are invisible to conventional light microscopy. In PALM, Betzig linked fluorescent molecules to proteins in the feature he wanted to study, and then shined a light to stimulate them. The labeled molecules responded weakly, with only a small, widely separated percentage of the fluorescent molecules emitting a few photons. When the emitting molecules were farther than 200 nm apart, each produced a single, highly localized bright spot on the image. Betzig then stimulated and imaged the sample over and over again, hundreds of times, to build a mosaic of sub-200 nm detail.

The new lattice light-sheet technique is also based on a Bessel beams method the Janelia group introduced in 2011. Bessel beams are nondiffracting wave patterns, vanishingly-thin rings of light produced by shining a laser through an annular mask. These beams keep their shape, and don’t spread out as they propagate, allowing researchers to generate extremely thin sheets of light.

In their new paper, Betzig’s team says that they have “crafted ultrathin light sheets.” Crafted is the right word: they shape the light the way a carpenter turns, shaves, and carves a baulk of lumber into a graceful table leg.

First, the laser beam is squeezed and stretched into a thin vertical line. Then it is bounced off a spatial light modulator (SLM)—an ultra-fast LCD that flashes a series of black-and-white patterns that reflect the incoming stripe of laser light back in a defined lattice of high and low intensity. (The SLM is the main feature distinguishing the lattice sheet method from its Bessel beam predecessor.) The reflected pattern passes through a thin transform lens, which throws a Fourier transform of the pattern onto the annular Bessel beam mask. The light then bounces between galvanometer-controlled mirrors that determine where the nodes of the lattice will fall in the light sheet. Only then does the beam pass through a lens to be focused into the sample, producing a hexagonal pattern of illuminated dots that spread in a sheet right and left of the beam. If the pattern is chosen wisely, interference effects actually sharpen the definition of the points, increasing resolution.

A piezoelectric stage moves the sample incrementally through the light sheet, which activates fluorescent markers in an ultrathin slice of the sample.

The lattice light-sheet device works in two modes—structured illumination microscopy (SIM) for high spatial resolution and “dithered” for better time resolution. SIM can resolve features in the 150-280 nm range. In the high-speed dithering mode, the lattice is swept across the sheet faster than the camera’s exposure time, illuminating a whole slice in a single step to reduce the number of steps necessary to photograph an entire volume. Dithered mode functions at 100 frames per second—about 7.5 times faster than SIM mode but, at  at 230-370 nm, it only has two-thirds SIM’s resolution.

No matter how kindly intended, a flood of photons pouring into a cell can injure or kill it—especially if it is dividing or otherwise vulnerable. The lattice light-sheet technique doesn’t do that. “The chief benefit of lattice light-sheet excitation… is its exceptionally low photobleaching and phototoxicity,” the researchers write. Each of the examples presented in the paper “was distilled from tens or hundreds of thousands of raw 2-D images,”  a figure one or even two magnitudes higher than the number of exposures allowable with other light methods.

The research produced remarkable images from a large collection of experiments conducted in collaboration with colleagues from 14 other groups around the world. Here are just a few of them:

  • Repeatedly imaging a non-living fixed sample to localize 4.2 million individual proteins in the nucleus’ membrane to within 8 to 45 nm.
  • Tracking single molecules of the protein that marks the ends of growing microtubules, the fibers that latch onto and reposition the replicating chromosomes during cell division, to build a comprehensive dynamic map of their growth [image above]. 
  • Keeping the light sheet stationary to follow extremely rapid changes in a protozoan at more than 300 frames per second, including stop-action images of moving cilia that could allow biologists to calculate the force each of the tiny tails generates.
  • Filming details of key stages in the development of live fruit fly embryos in unprecedented detail.

The researchers have patented the lattice light-sheet microscopy system. They’ve licensed it to microscope maker Zeiss and will also share the detailed instructions to researchers who wish to build their own instruments.

Where many scientific abstracts close with a guarded boast about future potential, this one ends:  “The results provide a visceral reminder of the beauty and complexity of living systems.”

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Rapid muscle contractions in a C. elegans embryo in the three-fold stage, with labeled GFP-PH domains (green) and mCherry-histones (magenta), as recorded in a single 2D optical section at 50 frames/sec. Scale bar, 10 um. (Video: Betzig Lab/HHMI)
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Samsung Demos Multi-Gbps Speeds Using 60 GHz Wi-Fi

Samsung has announced that it plans to bring a new multi-gigabit-per-second wireless technology to consumer devices as soon as next year. The technology is an implementation of the IEEE 802.11ad standard, operating in the 60 gigahertz frequency band. The company said the technology supports data transmission rates of up to 4.6 Gigabits per second, or about five times as fast as current Wi-Fi systems. 


Operating at a much higher frequency than standard Wi-Fi, which uses the 2.4 GHz and 5 GHz bands, the 60-GHz wireless connections would let users share data and stream movies between connected devices much faster. With a speed of 4.6 Gbps you can send a 4-gigabyte movie from your computer to your TV in less than 7 seconds. 

But the 60-GHz signals are also much easier to disrupt, failing to propagate through walls and losing signal integrity after just a few meters. This means that the 802.11ad technology, which some call WiGig, won’t replace your conventional Wi-Fi routers anytime soon. When it comes to device-to-device connections like those between a computer and a TV, though, the technology could provide a welcome speed boost.

In a press release, Samsung boasted that it has improved on the technology for consumer use by allowing multiple devices to connect to a 60-GHz network without interfering with one another. Isolating those channels, the company said, has helped improve the speed of the 60-GHz connections. 

Advances in beam-forming technology are also helping Samsung make the technology ready for market. Precision steered beams can avoid interference and signal blockages, ensuring that a tablet can maintain a connection with a home entertainment system, for instance, even if the user is walking around their living room.

Other technologies (including ultra-wideband and WirelessHD) have been proposed to connect devices wirelessly, but none has become widely used in consumer products. The Wi-Fi Alliance, the trade group that promotes Wi-Fi standards, adopted WiGig into the fold  in 2013. It says the technology could be useful not only for streaming video but also for connecting devices like laptops to external monitors and keyboards without a nest of cables and connectors. Last year, Dell released a 60-GHz wireless laptop and docking station combo that allows for exactly that.

Samsung expects to incorporate the 802.11ad standard into a variety of devices next year, including entertainment gear and medical equipment. In the long term, the company also expects that the technology will also find applications in smart home technology, connecting a wide variety of devices over larger areas as the technology matures.

XPrize Announces Finalists Building Next-Gen Medical Sensors

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Today’s home medicine kit is fairly limited when it comes to diagnostics: You can take your temperature, check your blood pressure, and give yourself a home pregnancy test, but that’s about it. The Nokia Sensing XChallenge (from the XPrize folks) aims to improve that situation by spurring inventors to create portable gadgets that consumers can use to collect accurate, real-time health information. The 11 finalist teams, announced today, are building gadgets that do lab tests, monitor heart disease, check vital signs, and more. 

The Sensing XChallenge is distinct from a very similar competition, the Qualcomm Tricorder XPrize, in which teams are vying to create a universal diagnostic tool along the lines of the handheld tool wielded by Star Trek’s Dr. McCoy. In the Tricorder contest, the devices are required to diagnose a specific list of 15 ailments, whereas in the sensing challenge the tools can be designed to do just about anything.   

However, the XPrize doesn’t see redundancy here, but rather a symbiotic relationship, says Grant Campany, senior director of the sensing challenge. The Nokia contest is intended to reward teams for developing technologies that could be incorporated into a Tricorder device, he told IEEE Spectrum in an email. Several sensing teams are validating technologies for collaborating Tricorder teams, Campany says, which are racing to build at least 30 working Tricorder devices for consumer testing next year.

The Nokia contest’s judges will have some apples vs. oranges decisions to make, because the 11 finalists’ gadgets are designed for a wide variety of applications. How do you compare a handheld spectrometer, which can detect biomarkers of liver function in a drop of blood, to a pressure sensor implanted in the pulmonary artery of a heart disease patient? Other devices include a wearable sensor to detect sleep apnea, a mobile phone-based imaging app to find symptoms of eye disease, and a variety of mobile lab gadgets. Which among these is the most meritorious, and therefore worthy of the $525,000 grand prize? 

Campany says the judges have a list of criteria that include technical innovation, reliability, ease of use, and relevance to a public health need. He also notes that crowd voting accounts for 10 percent of the teams’ scores; you can cast your vote for the winner through the end of the month. The winning team will be announced in November at the Exponential Medicine conference. 


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