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Jellyfish-Inspired Microchip Captures Cancer Cells

 

   The mesmerizing movements of jellyfish have inspired researchers to design all sorts of things, from mechatronic jellyfish that function as autonomous robots to artificial jellyfish built from rat cells and silicone. Now scientists have built a jellyfish-inspired microchip that can capture cancer and other rare cells in human blood.

A jellyfish captures floating food particles with its long tentacles, which are equipped with repeating patterns of sticky structures. Researchers at Brigham and Women's Hospital in Boston used that design concept to build a microfluidic chip coated with long strands of repeating DNA sequences that bind to specific proteins on cancer cells as they float by in the blood.

Capturing cancer cells in the blood stream can provide key information about how a tumor is responding to treatment, and a device like the jellyfish chip could be used not only in diagnosing and monitoring cancer, but also for capturing other rare cells in the blood, such as fetal cells, viruses and bacteria, the researchers reported yesterday in the journal Proceedings of the National Academy Sciences.

Other microfluidic devices that rely on antibodies or engineered nucleic acids have been developed in the past with a similar intent, but have failed to capture large entities in the blood, such as whole cells. The new jellyfish-like device can grab those cells, and more of them. The key was making the three-dimensional DNA strands long, like tentacles, and arranging them in a herringbone pattern inspired by the repeating patterns of sticky structures on the jellyfish. And unlike previous methods, the device can also easily release the cells so that they can be studied in the lab.

In addition to diagnostic applications, the device could also be used therapeutically. "What most people don't realize is that it is the metastasis that kills, not the primary tumor," says Jeffrey Karp, an author of the paper and a bioengineer at Brigham. "Our device has the potential to catch these cells in the act with its 'tentacles' before they may seed a new tumor in a distant organ."

Go jellyfish. Maybe researchers should spend more time at the aquarium staring at these hypnotic marine animals.

Image: Brigham and Women's Hospital

Hurricane Sandy’s Radio Days

My son rarely listens to “real” radio; he’s more likely to be listening Pandora on his iTouch. When we’re in a hotel, he scrambles for the iPod dock, not a favorite radio station. But I think he—and I—got a new appreciation for radio in the wake of Hurricane Sandy, when we traveled for a family wedding to a storm-struck, electric-powerless region of New Jersey two weeks ago.

The Internet didn’t work, cell phone coverage was spotty, and TVs had gone dark. We stayed at my mother’s house, where her land line telephone worked just fine. But I couldn’t call to check on my elderly aunt; Verizon had upgraded her to its fiber network, and without power in her house, that was useless. The entire region, it seemed, was dark, cold, and silent—except for radios.

My mother has an ancient boombox in her kitchen—with a slot for (way too many) D batteries. She was ahead of the game. As the storm threatened, FEMA Administrator Craig Fugate, on CBS This Morning urged the up to 50 million people living in areas meteorologists predicted would be impacted by the storm to stay informed by tuning into local broadcasting, radio in particular. "Probably one of the things you don't really think about anymore is having a battery powered radio or a hand-cranked radio to get news from your local broadcasters…" Fugate said. "Cellphones may be congested. Radio is oftentimes the way to get those important messages about what's going on in the local community."

My aunt hadn’t heard Fugate’s advice; she figured out for herself that she’d need a battery operated radio. She hunted through stores, ending up with a jogging radio on an armband (and her very first pair of earbuds). It wasn’t quite what she had in mind, but it kept her informed throughout an entire week without power.

People who failed to get a battery operated radio before the storm hunted in vain afterwards. Hunkered down to watch election results in a local bar where power had been restored, I talked to one gentleman who was taking a break from his ongoing search for a battery operated radio. He was getting particularly desperate, figuring he’d be wanting to listen to election news long after the bar closed. (Fortunately for him, the presidential race was called well before closing time.)

And indeed, if you did have a battery-operated or hand-cranked radio (I’m never making fun of those NPR pledge gifts again), you did have something to listen to, because, by and large, radio stations stayed on the air. Radio towers are designed to be hurricane-proof, with backup power for eight to 10 days. (That’s something the cell networks could learn from: post Katrina, the Federal Communications Commission (FCC) had proposed that cell towers be required to have backup power, but the cellular industry resisted, citing the high cost. Post Sandy, one in four cell sites in the affected region failed. So folks used to turning to their smartphones to find out what’s going on were pretty much out of luck.)

Though radio stations, for the most part, were prepared with generators and backup generators, a few did go down.  New Jersey Broadcasters Association President and CEO Paul Rotella told Radio World that “If you have 10 feet of water, a station will go down. But if a station does go down, it doesn’t matter so much because one station alone can reach millions of people. So if you have hundreds of stations and one goes down, people are going to hear it, they are going to get their information. That’s what the ubiquitous nature of radio is all about.”

Rotella called for cell phone manufacturers to include FM chips in cell phones, or to enable chips already installed in the case of emergencies. He’s not the only one arguing for FM chips in phones; some are looking to Congress to mandate the chips' inclusion as a safety issue. Jeff Smulyan, CEO of Emmis Communications, an owner and operator of radio and television stations, has long been lobbying for such a requirement, and the FCC is starting to see things his way

Again, the cellular companies are resisting—people listening to Internet radio through cell phones pay for that data stream.

I’m rooting for Smulyan, Rotella, and their compatriots. Put those FM chips in a cell phones; we can charge them from our car batteries if the power is out; we won’t have to grope around on closet shelves to find them in a blackout since they’re likely to be in our pockets; and, the next time a hurricane is bearing down people like my aunt and the guy in the bar, they won’t have to scramble to find battery operated radios.

If you have power and Internet, follow me on Twitter @TeklaPerry. (And thank you to the National Association of Broadcasters for pointing me to some of the information used in this post.)

Answers from Mars

Mars: the planet that keeps on giving.

The successful summer landing of NASA’s Mars Science Laboratory (MSL), Curiosity, captured the world’s imagination, provided a steady stream of new discoveries, and spawned a series of TV documentaries on the National Geographic and Discovery channels.

This week, NOVA’s Ultimate Mars Challenge—airing Nov. 14 on PBS at 9pm (ET)—joins the fray, not only chronicling the engineering necessary to make the landing, subsequent exploration, and scientific discoveries possible, but placing it in context with preceding Mars missions. (The program spells out what we learned from past missions that informs the current one, as well as what we hope to learn from this one that, budgets allowing, will inform the next.)

“One of the reasons Mars is still exciting is because it hasn't turned out to be a boring story at all,” said MSL project chief engineer Rob Manning during a NOVA press conference. “Every time we've turned a page, we've learned something more rich about this planet, that maybe there's something more to go. Now, we're going to start exploring Mars over the coming two Earth years. And a lot of it is, `What are we going to learn?’ And of course, we'll have to debate and duke it out with everyone else to figure out the right thing to do with limited resources.”

Challenge producers Gail Willumsen and Jill Shinefeld culled more than 60 hours of raw NASA footage and their own interviews for the hour-long documentary. They note that getting the project finished was a challenge. With discoveries continually flowing in from Curiosity, they were making changes right up to the day they needed to submit it to NOVA.

Billions of years ago, “Mars and Earth had similar conditions for life,” says Willumsen, who also directed the documentary. “It arose on Earth, but we don’t know if it arose on Mars. What we do know is that Mars changed radically: something happened and it went in a different direction. The exciting thing about the landing site, Gale Crater, is that it has Mount Sharp, which is a mountain of layered rock that is a chronology of Mars’ history. So they’re going to, theoretically, go through and read those layers and perhaps find out why it became the cold, dry planet of today. It’s a massive form of climate change.”

Among the more frustrating decisions the pair had to make in streamlining the documentary's focus, was cutting one interview with Nathalie Cabrol, a senior research scientist at the SETI Institute in Mountainview, Calif. 

“The thing she said that really struck me was that the need to explore is rooted in all of life, not just Homo sapiens,” says Willumsen. “The impulse to explore is part of the survival instinct.”

 

Artificial Skin Can Feel and Heal

Stanford University announced Monday that a team of chemists and engineers created a flexible, self-healing, conductive material. Led by chemical engineering professor Zhenan Bao, the researchers combined a plastic consisting of chains of molecules joined by hydrogen bonds, with rough nanoparticles of nickel that one of the researchers, Benjamin Chee-Keong Tee, describes as mini-machetes. The bumpy edges, Tee said, concentrate the electrical field and make it easier for current to flow from one particle to the next. Twisting or pressing on the material changes the distance between the metal particles and therefore the resistance; such changes can be translated to measurements of pressure.

When sliced with a scalpel and then pressed back together, the material recovers 75 percent of its mechanical strength and electrical conductivity in seconds; 100 percent in about half an hour.

The team envisions prosthetic arms that can detect the pressure of a handshake or the degree of bend in a joint, as well as electrical wires that can repair themselves when broken.

Caption: A researcher cuts a piece of the self-healing "skin". Photo: Stanford University.

Mirror, Mirror, On the Wall, Who's the Fastest of Them All?

The unveiling of Oak Ridge National Laboratory’s Titan Cray XK7 supercomputer knocks every other computer in the world down one notch in the Petaflop Hall of Fame. The Top500 Supercomputer Sites website has just posted new rankings noting that there are now 23 systems with performance better than a petaflop per second, “just four-and-a-half years after the debut of Roadrunner, the world’s first petaflop/s supercomputer.” (Los Alamos National Laboratory's Roadrunner is now 22nd on the list.)

Top500’s 12 November announcement  includes an analysis of today’s trends in supercomputing. Some highlights:

  • Multi-core systems dominate, and more systems (including Titan) are using processor/co-processor architectures.
  • Intel provides 76 percent of the supercomputer processors, followed by AMD (12 percent) and IBM (10.6 percent).
  • The threshold for membership in the Top 100 list has moved up to 241.3 teraflop per second, up from 172.7 Tflop/s just six months ago.

So here are the world's 10 most powerful supercomputers—for now: 

  • Titan (Cray XK7)—Oak Ridge National Laboratory, USA:  560 640 cores, 17 590 teraflop per second, 8 209 kilowatts.
  • Sequoia (IBM BlueGene/Q)—Lawrence Livermore National Laboratory, USA:  1 572 864 cores, 16 325 Tflop/s, 7890 kW
  • K computer (Fujitsu K computer)—RIKEN Advanced Institute for Computational Science, Japan:  705 024 cores, 10 510 Tflop/s, 12 660 kW
  • Mira  (IBM BlueGene/Q )—Argonne National Laboratory, USA: 786 432 cores, 8162 Tflop/s, 3945 kW
  • JUQUEEN (IBM  BlueGene/Q)—Forschungszentrum Juelich (FZJ), Germany: 393 216 cores, 4141 Tflop/s, 1970 kW
  • SuperMUC (IBM iDataPlex DX360M4)—Leibniz Rechenzentrum, Germany:  147 456 cores, 2897 Tflop/s, 3423 kW
  • Stampede  (Dell PowerEdge C82207)—Texas Advanced Computing Center, USA: 204 900 cores, 2660 Tflop/s , (power n/a)
  • Tianhe-1A ( NUDT YH MPP)—National Supercomputing Center in Tianjin, China: 186 368 cores, 2566 Tflop/s,  4040 kW
  • Fermi  (IBM BlueGene/Q)—CINECA, Italy:  163 840 cores, 1725 Tflop/s, 822 kW
  • DARPA Trial Subset  (IBM Power 775)—IBM Development Engineering, USA:  63 360 cores, 1515 Tflop/s, 3576 kW

See the Top500 site for the full list, highlights, analysis and a poster showing the evolution of big iron.

Images: Titan, Oak Ridge National Laboratory (top). Sequoia, IBM

Your Unconscious Brain Can Do Math, Process Language

The unconscious brain may not be able to ace an SAT test, but new research suggests that it can handle more complex language processing and arithmetic tasks than anyone has previously believed. According to these findings, just published in the Proceedings of the National Academy of Sciences, we may be blithely unaware of all the hard work the unconscious brain is doing. 

In their experiments, researchers from Hebrew University in Israel used a cutting-edge "masking" technique to keep their test subjects from consciously perceiving certain stimuli. With this technique, known as continuous flash suppression, the researchers show a rapidly changing series of colorful patterns to just one of the subject's eyes. The bright patterns dominate the subject's awareness to such an extent that when researchers show less flashy material to the other eye (like words or equations), it takes several seconds before the brain consciously registers it. 

This masking technique is "a game changer in the study of the unconscious," the scientists write, "because unlike all previous methods, it gives unconscious processes ample time to engage with and operate on subliminal stimuli."

To study the unconscious brain's ability to process language, the researchers subliminally showed the subject short phrases that made variable amounts of sense: For example, subjects might see the phrase "I ironed coffee" or "I ironed clothes." The researchers gradually turned up the contrast between the phrase and its background, and measured how long it took for the phrase to "pop" into the subject's conscious awareness. As the nonsensical phrases popped sooner, the researchers hypothesize that the unconscious brain processed the sentence, found it surprising and odd, and quickly passed it along to the conscious brain for further examination.  

To determine the unconscious brain's mathematical abilities, the researchers presented a simple subtraction or addition equation (for example, "9 3 4 = ") to a subject, but took it away before it could pop into consciousness. Then they stopped the masking pattern and displayed a single number, asking the viewer to pronounce the number as soon as it registered. When the number was the answer to the subtraction equation (for example, "2"), the subject was quicker to pronounce it. The researchers argue that the viewer was "primed" to respond to that number because the unconscious brain had solved the equation. Oddly, they didn't find the same clear effect with easier addition equations. 

Why is IEEE Spectrum covering this? We could argue that until we understand the workings of consciousness in the human brain, we'll never be able to build an artificial intelligence that can be described as conscious and aware. Or we could admit that we just thought the study was nifty. 

Images: Wikimedia Commons; Ran Hassin et al. 

Membrane Mixes Materials to Measure Nanogram Masses, Temperature Simultaneously

The potential of thin film bulk acoustic wave resonators (FBARs—no sniggering from the back row, please) to measure mass at the nanogram level has marred by one persistent obstacle.

FBAR sensorAn FBAR membrane is electronically driven to vibrate at a characteristic resonant frequency. When a particle—a protein molecule, perhaps—adsorbs to membrane, the resonant frequency drops; the frequency change is proportional to the glued-on mass. So, measure the frequency drop, measure the mass. And because the frequency shift for a given mass is proportional to the square of the initial resonant frequency, the higher the initial resonant frequency, the more sensitive the measurement and the smaller the mass you can expect to measure.

And now for the obstacle. The FBAR’s acoustic characteristics change significantly with temperature. The speed of sound changes, and so does the thickness of the membrane. And this temperature sensitivity grows along with its measurement sensitivity as the resonant frequency climbs.

Up until now, solutions to this gravimetric problem have required two separate measurements—either measuring the frequency change in two distinct environments (an isolated test environment and the field environment) or building a second temperature sensor into the device.

But a collaboration among researchers from four British Universities (Cambridge, Manchester, Sheffield, and Bolton) and from Korea’s Kyung Hee University—has yielded a new twist on an old solution to the problem of temperature effects on precise measurement.

Harrison's GRidiron PendulumTemperature changes have dogged metrologists at least since John Harrison labored through much of the 18th Century to construct the first accurate clocks. Balance springs sag as temperatures rise. Iron pendulum rods stretch.  Time seems to slow down as the weather warms up.  The solution is to combine materials to counteract these effects. Harrison devised a “compensation curb” (similar to the bimetallic spring at the heart of many home thermostats) to “rewind” the balance spring as temperatures rose. He also invented the gridiron pendulum, in which brass or zinc compression beams lift the pendulum weight to counteract the iron rod’s expansion. (See Dava Sobel’s Longitude or this Royal Society inventory of Harrison’s innovations.)

Though others had suggested a Harrisonian two-material solution to FBARs’ problems, this is the first time it’s been made to work over a broad range of real-world temperatures. To do this, Cambridge’s Luis Garcia-Gacendo and the team built a two-material device that resonates in two characteristic modes—arranged so that one of the composite's resonant modes increases in frequency as temperature rises while the other decreases in frequency. By measuring the shifts in both modes simultaneously, scientists can calculate both the temperature at the device and the mass of adsorbed particles.

The prototype FBAR device “for parallel sensing of temperature and mass loading” consists of a 2-micrometer-thick piezoelectric film of crystalline zinc oxide sputtered onto a 2 μm layer of silicon dioxide, which sits atop a silicon wafer sandwiched between chromium-gold electrodes. The prototype measurement tool showed native resonant modes at 754 megahertz and 1.44 gigahertz. Both silicon dioxide and zinc oxide expand with temperature (though at different rates), so both layers get thicker as the temperature rises. This would normally mean that the resonant frequencies of both modes would fall with temperature. In this case, though, rising temperatures cause the acoustic wave velocity to increase in the silicon dioxide layer and decrease in the zinc oxide layer. So a one-Kelvin change in temperature causes a 79.5 parts per million frequency increase in the SiO2 and a 7 parts per million frequency drop in ZnO.

Thus, measuring frequency changes in both modes simultaneously indicates both temperature and mass.

The team successfully measured loads of human fibrinogen and bovine serum albumin in concentrations of about 1 to 1000 micrograms per milliliter (The total mass measured is unstated; the calibration tests measured masses on the nanogram level). Note, though, that the protein solutions were deposited on the membrane and then dried. The device as built relies on thickness longitudinal mode data, and cannot be applied to direct sensing of masses in liquids. The authors note, however, that repositioning the electrodes could enable thickness shear mode sensing in a successor device, opening up, for example, opportunities for direct sensing in biological or biotechnology applications. 

Images: Top: L. Garcia-Gacendo, Cambridge University. Bottom: Public Domain.

Oak Ridge Unveils 20-Petaflop ‘Titan’ Supercomputer

Partially overshadowed by the dislocations of Hurricane Sandy was Oak Ridge National Laboratory’s unveiling of its Titan supercomputer, a 20-petaflop Cray XK7 that will crunch massive numbers to run simulations  in materials science, combustion, and, appropriately, climate change. (In the shadow of the storm, it’s interesting to note how many of Titan’s non-weather applications also have environmental implications.)

The system contains 18,688 nodes, each containing a 16-core AMD Opteron 6274 CPU and an NVIDIA Tesla K20 graphics processing unit. The design is 10 times as powerful as ORNL’s previous supercomputer, the Jaguar, but it fits into the same space and uses only a little more power.

“Combining GPUs and CPUS in a single system requires less power than CPUs alone, and is a responsible move towards lowering our carbon footprint,” said ORNL associate director Jeff Nichols in the debut announcement. Titan’s 299,008 CPUs will guide the complex simulations, while the even faster multi-core GPUs will handle the details.

It will take a while before Titan finishes acceptance testing. When it goes online, its biggest client will be the Department of Energy’s INCITE (Innovative and Novel Computational Impact on Theory and Experiment) program.

The biggest-iron to-do list includes:

  • Calculating nanoscale magnetic properties and temperature sensitivities of steels, nickel-iron alloys, and advanced permanent magnets using Wang-Landau locally self-consistent multiple scattering (WL-LSMS) methods.
  • Modeling combustion in the turbulent environment of an internal combustion engine—potentially important to improving engine designs that will both conserve fossil fuel resources and reduce greenhouse gas production.
  • Modeling the behavior of neutrons in a nuclear power reactor—part of a study intended to help extend the working lives of aging reactors that still provide about 20% of America’s power. (ORNL says Titan will be able to simulate one fuel-rod service cycle in 13 hours, less than a quarter of the time Jaguar needed.)
  • Simulating the long-term evolution of the world’s climate, helping to anticipate future air quality and the behavior of suspended particles. The simulation will reduce the world to an array of 14x14 km cells, “imagining” five years of real time per day of computing time. (Jaguar could simulate just three months in a day of calculation.)

Using the Inner Ear's Biological Battery

Scientists have harvested energy from a guinea pig's inner ear and used it to power a small wireless transmitter. With further design work, researchers could harvest this biological battery to power implanted devices near the human ear, such as molecular sensors and drug delivery vehicles for hearing loss and other disorders, according to a study to be published today in Nature Biotechnology.

It has been known for decades that the inner ear contains this biological battery, but until now, no one has harvested it. The authors of the paper, led by Anantha Chandrakasan at Massachusetts Institute of Technology and Konstantina Stankovic at Massachusetts Eye and Ear Infirmary, succeeded without damaging the guinea pigs' hearing. 

The inner ear's biological battery is located in a spiral-shaped auditory region called the cochlea. The electric potential in this region arises from the electrical difference between two different chambers in the cochlea, which contain charged particles such as potassium and chloride ions. A nearby specialized structure known as the stria vascularis transports the ions through its unique arrangement of electrogenic ion pumps, generating an electrochemical potential known as the endocochlear potential

At 70-100 mV, the electrochemical potential of the inner ear is the highest in the mammalian body. But it's still a very small amount of energy, and only a fraction of it can be extracted without disrupting hearing. To address this challenge, the researchers chose to power a specially designed chip equipped with an ultralow-power radio transmitter. 

In the experiments, the researchers implanted electrodes in the cochlea of anesthetized guinea pigs. The electrodes were connected to the chip, which was located outside the animals' ears. (It is small enough to fit in a human ear.) The chip included power-conversion circuitry that gradually builds up charge in a capacitor. To kick-start the control circuit, the researchers applied a one-time burst of radio waves. The device wirelessly transmitted measurements of the endocochlear potential to an external receiver. About 1 nW of power was extracted for up to 5 hours—long enough to enable the 2.4 GHz radio to transmit measurements every 40-360 seconds.

Harvesting energy from the human ear to power small electronic devices could be a huge breakthrough for people grappling with hearing loss and other disorders. Implantable electronics usually require large energy reservoirs to operate reliably over long periods of time. But human anatomy limits the size of implantable batteries, and often requires surgical re-implantation or cumbersome external wireless power sources. Harvesting enough energy from the body's own energy sources is a way to extend implant life, and maybe even allow it to operate autonomously, the authors report.

Images: Patrick P. Mercier

 

Lung-on-a-Chip Used to Model Human Disease

A lung-on-a-chip looks nothing like a human lung: It's a clear, flexible piece of silicone rubber that's smaller than your thumb, with human lung cells growing inside the microscopic channels carved into it. But researchers have shown that this gizmo can not only mimic the essential functions of a healthy human lung, it can also be used to reproduce the conditions inside a diseased lung. This proof-of-concept research shows that organ-on-a-chip devices can aid medical research and drug development, and may reduce the need for animal testing in the future. 

The researchers hail from Harvard's Wyss Institute for Biologically Inspired Engineering, which is at the forefront of organ-on-a-chip research. We've covered prior triumphs from the Wyss researchers like their gut-on-a-chip, which mimicked human intestines and came complete with peristaltic motions, and their plans to link together ten different organ-chips to create a "human-on-a-chip." They describe their latest advance in the journal Science Translational Medicine

The lung-on-a-chip is fabricated using techniques learned from computer microchip manufacturing. Its channels have a porous matrix in the middle that host lung cells on one side, where air flows over them, and capillary cells on the other side, where a blood-like fluid flows over them. Vacuum pumps on both sides of the chip cause it to expand and contract, mimicking the way the human lung's air sacs expand and contract with every breath. 

In the latest research, the scientists reproduced the symptoms of pulmonary edema, a potentially deadly condition characterized by fluid and blood clots in the lungs. The cancer chemotherapy drug interleukin-2 (IL-2) is known to cause pulmonary edema in some patients, so the researchers introduced IL-2 into the lung-on-a-chip and watched to see what happened. Just as in a real lung, on the chip the drug caused fluid and proteins to cross over the matrix and leak into the air flow channel.

The researchers also tested a new class of drug that's being developed by GlaxoSmithKline to treat pulmonary edema symptoms. The drug was effective on the chip, and in a separate study the pharmaceutical scientists validated the results in animal experiments. These results suggest that organ-on-chip technology could soon reduce the need for animal testing, which is expensive, slow, and controversial. 

Donal Ingber, founding director of the Wyss Institute and a senior author of this study, spoke in a press release about the utility of this cutting-edge technology:

"In just a little more than two years, we've gone from unveiling the initial design of the lung-on-a-chip to demonstrating its potential to model a complex human disease, which we believe provides a glimpse of what drug discovery and development might look like in the future."

Images: Wyss Institute

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