Tiny Magnets Could Clear Diseases from the Blood

BIOMEDICINE

Tiny Magnets Could Clear Diseases from the Blood

Researchers make magnetic nanoparticles that can latch on to harmful molecules and purge them from the blood.

• MONDAY, NOVEMBER 28, 2011
• BY ADAM MARCUS

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Researchers in Zurich, Switzerland, are developing nanomagnets that could someday strip potentially harmful substances from the blood. The technology might be used to treat people suffering from drug intoxication, bloodstream infections, and certain cancers.

The project involves magnetized nanoparticles that are coated with carbon and studded with antibodies specific to the molecules the researchers want to purge from the blood: inflammatory proteins such as interleukins, or harmful metals like lead, for example. By adding the nanomagnets to blood, then running the blood through a dialysis machine or similar device, the researchers can filter out the unwanted compounds.

"The nanomagnets capture the target substances, and right before the nanoparticles would be recirculated, the magnetic separator accumulates the toxin-loaded nanomagnets in a reservoir and keeps them separated from the recirculating blood," explains Inge Herrmann, a chemical engineer at the University of Zurich who is leading the work.

According a study published in the journal Nephrology Dialysis and Transplantation in February 2011, the researchers were able to remove 75 percent of digoxin, a heart drug that can prove fatal if given in too high a dose, in a single pass through a blood-filtration device. After an hour and a half of cleansing, the nanomagnets had removed 90 percent of the digoxin.

One big caveat is that the researchers must demonstrate that the particles aren't toxic to the body and won't interfere with the blood's ability to clot. But early results are promising. In a 2011 paper in Nanomedicine, Herrmann's group showed that the nanomagnets did not damage cells or promote clotting—two critical safety milestones.

At the annual meeting of the American Society of Anesthesiologists in October, Herrmann presented data showing that the nanomagnets are partially taken up by monocytes and macrophages, two forms of immune cells. That's an important proof of principle for any future application of the technology in fighting serious infections.

Herrmann and her colleagues are now conducting a study of the technology in rats with sepsis—a severe bloodstream infection marked by the massive buildup of damaging immune molecules. Severe sepsis affects approximately a million people in the United States each year.

Jon Dobson, a biomedical engineer at the University of Florida, says detoxification is "a really interesting application" of nanotechnology. His own group has been using magnetic nanoparticles as remote controls to manipulate cellular activity, such as the differentiation of stem cells. "With chemicals, once the process starts, it can be difficult to switch it off. With magnetic technology, you can switch it on and off at will," Dobson says.

The potential uses of the Swiss group's method might extend beyond sepsis to other diseases, including blood cancers, Dobson says. For example, it might be possible to design nanomagnets that pair up with circulating leukemia cells and usher them out of the body, thus reducing the risk of metastasis.

O. Thompson Mefford, a nanotechnology expert at Clemson University, says the approach has appeal. He notes that the human body is a highly oxidative environment, and oxidation of iron weakens the magnetic properties of the material. By coating their magnets in carbon, the Swiss group may have come up with a way to prevent this corrosion.

Still, he says, the viability of the technique remains to be seen: "Having high circulation times, no immune response, and having the magnets not cluster with each other, that's a real challenge."

Fluorescent Spray Could Help Surgeons Identify Cancer Quickly

BIOMEDICINE

Fluorescent Spray Could Help Surgeons Identify Cancer Quickly

Researchers develop a spray that could make cancer cells glow within a minute of application.

• TUESDAY, NOVEMBER 29, 2011
• BY ERICA WESTLY

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http://www.technologyreview.com/biomedicine/39192/?mod=chfeatured

Cancer surgeons strive to remove cancerous cells while preserving as much healthy tissue as possible. Unfortunately, cancer cells are notoriously difficult to identify visually.

A group led by the National Cancer Institute's Hisataka Kobayashi has developed a fluorescent spray that can label cancer cells within a minute. The hope is that surgeons could apply it during or after a procedure to catch any cancer cells they might have missed.

Several research teams have been working on fluorescent labels for cancer cells that could serve as a visual guide for surgeons, but other methods typically take much longer to work.

The researchers demonstrated the spray's ability to label cancer cells in mice in a study published last week inScience Translational Medicine. The fluorescence is activated by an enzyme called y-glutamyl transpeptidase that is abundant in tumor cells but not in normal cells. The probe that Kobayashi and his team designed contains a chemical target of the tumor enzyme. The enzyme cleaves the chemical on contact, and this activates the fluorescence signal.

Because the enzyme sits on the cell surface, this reaction occurs within seconds. Fluorescence probes that target molecules inside cancer cells can take several hours or sometimes days to build up enough of a signal. "A probe that is fast like this could really benefit surgeons in the operating room," says Michael Bouvet, a cancer surgery expert at the University of California, San Diego. Bouvet coauthored an editorial accompanying the study. "Even when you think you've taken out all of the primary tumor, you'd be surprised by how much cancer is often left behind."

Bouvet says the spray approach could be particularly beneficial for ovarian and colon cancers, which can spread into the surrounding cavities, making surgical removal more challenging. While it is possible to label cancer cells with fluorescence in advance, being able to apply the dye locally requires a much lower dose than injection or oral administration—about 1,000 to 10,000 times lower, according to Kobayashi—which would help allay toxicity concerns.

Not all cancer cells express the enzyme that the spray targets, and, of the ones that do, only those that are actively growing express enough of it to be detected by the fluorescence. But that still leaves a good number of clinical applications, including many types of ovarian, cervical, gastric, and colon cancers.

Kobayashi's team has already begun to evaluate the spray in human tumor samples. It expects to start full clinical trials in a few years. 

EEG Detects Signs of Awareness in Vegetative Patients

http://www.technologyreview.com/biomedicine/39123/?p1=A1

BIOMEDICINE

EEG Detects Signs of Awareness in Vegetative Patients

Researchers develop a simple way to test whether patients who appear unresponsive truly are.

• THURSDAY, NOVEMBER 10, 2011
• BY EMILY SINGER

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Three brain injury patients diagnosed as being in a vegetative state—meaning they do not respond to their environment—may actually be conscious. Using EEG (electroencephalography) to measure their brain activity, researchers found that the patients could follow simple commands.

This supports previous findings from the same group suggesting that some people who appear outwardly unresponsive may have a relatively high level of cognitive capacity. Researchers aim to ultimately develop the approach into a communication tool.

In the study, researchers examined 16 patients with brain injury—some due to traumatic injury and others due to lack of oxygen—and 12 healthy people, asking both groups to imagine moving either their hands or toes while wearing an EEG monitor. They found that, like the healthy people, three of the brain injury patients could reliably generate two distinct brain activity patterns based on the command. One patient did it more than 200 times, which is even more than the healthy participants managed.

The team had previously used functional MRI, or brain imaging, to show that a patient diagnosed as being in a vegetative state could use a similar system to answer yes or no questions. That startling finding rocked the medical world, begging the question of how many of these patients had cognitive function beyond what their outward function indicated.

MRI machines are, however, expensive and largely limited to hospitals, making them a difficult tool to study brain injury patients, who are often in rehabilitation or nursing homes. In the new study, researchers used a standard EEG device, which is relatively inexpensive and highly portable. "It's probably about as sensitive as MRI," says Adrian Owen, a researcher at the University of Western Ontario, who led the study. "That means we have something we can get out into the community and use in hospitals or residential homes."

The researchers can detect when someone is thinking about moving a hand versus a toe because the brain activity originates in a different part of the motor cortex, the part of the brain that controls movement. Owen's team spent much of the last year working out how to accurately decode the electrical signals the brain emits when imaging these movements. Thefindings of the new study were published this week in The Lancet.

The three patients who could respond via EEG did not share any obvious features; they varied in age, in time since the original injury, and in the type of injury suffered. Owen's team is now using high resolution fMRI machines to study their brains in fine detail in hopes of finding some commonality. "Anything we can do to improve our understanding or to learn more about catastrophic brain injuries can help us understand what's going," says Owen.

They hope to eventually use the EEG setup to ask patients questions, which had been possible with fMRI. At the moment, researchers can't read the EEG response in real-time, making interaction very difficult. "Our priority now is trying to speed it up; then we'll move on to communication," he says. 

What exactly the new findings indicate about the patients' level of consciousness is still controversial. "I think they were entirely aware and conscious of what's going on," says Owen. "For them to do this, they have to have understood the instructions we gave them, to have sustained attention, to keep on task, and to respond. These are all things we associated with consciousness."

Morten Storm Overgaard, head of the Cognitive Neuroscience Research Unit at Aalborg Universit in Denmark, disagrees. "I think their study is very interesting, but it's hard to argue that there is link between command following and consciousness. And there's no independent way of making sure," says Overgaard, who wrote a commentary accompanying the paper. Overgaard does agree, however, that someone who can reliably answer questions via brain activity is likely conscious.

Both Overgaard and Owen say a new classification system is required to accurately reflect the state these patients are in. "While they do meet all the clinical criteria for the vegetative state, we know they are not actually vegetative," says Owen. One suggestion that has yet to catch on is "behavioral unresponsiveness syndrome."

A Versatile Touch Sensor

COMPUTING

A Versatile Touch Sensor

A new system adapted from a technology used for underwater cables could lead to touch sensors in clothes and coffee tables.

• TUESDAY, NOVEMBER 1, 2011
• BY KATE GREENE

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We live in an increasingly touchy-feely tech world, with various ways for smart phones and tablet computers to sense our finger taps and gestures. Now a new type of touch technology, developed by researchers at the University of Munich and the Hasso Plattner Institute, could lead to touch sensitivity being added to everyday items such as clothing, headphone wires, coffee tables, and even pieces of paper.

The new touch technology relies on something called time domain reflectometry, or TDR, which has been used for decades to find damage in underwater cables. TDR is simple in theory: send a short electrical pulse down a cable and wait until a reflection of the pulse comes back. Based on the known speed of the pulse and the time it takes to come back, software can determine the position of the problem—damage in the line or some sort of change in electrical conductance.

Patrick Baudisch, professor of computer science at the Hasso Plattner Institute, says engineers noticed in the 1960s that the technology could be used to indicate a touch of a wire. Recently, the ability to sense the short time delay over very short distances has gotten more accurate, which made it possible to use TDR for interactive applications.

The TDR implementation is straightforward, according to Raphael Wimmer, a student at the University of Munich who developed the new approach with Baudisch. For one demonstration, he taped two parallel strips of copper to a piece of paper. Metal clips connect the copper strips to a pulse generator and detector. Pico-second-long electrical pulses are sent out, and if there's any change in capacitance between the two strips of copper—produced by a finger close to or touching the wires, for instance—part of the pulse is reflected back.

An oscilloscope shows the changing waveform produced by the reflected pulse, and software on a connected computer analyzes the waveform to determine the position of the touch. The current setup is a bit clunky, Wimmer admits, but he says it should be feasible to shrink the pulse generation, detection, and position calculation onto a chip.

To make a surface touch-sensitive requires only two wires (or metal traces of conductive ink), which can be configured in various patterns to get the necessary coverage. In contrast, a capacitive touch screen like the one in the iPhone uses a matrix of wires coming out of two sides of the screen. "You have to route them to a controller in special ways, and that's quite complicated," says Wimmer. TDR avoids the engineering challenges of a traditional capacitive touch surface, he says.  

"Wimmer's application of TDR to touch is very clever," says Jeff Han, founder and CEO of Perceptive Pixel, a company that is developing large multi-touch displays. He suspects that it could provide new ways of detecting user input like touch sensing along an unmodified headphone cable, something that would be difficult to do with traditional sensors.

Over the next couple of months, Wimmer says, the researchers will be testing ways to shrink the TDR system design into a chip. He says he's also exploring the possibility of using light pulses in fiber optics as well as electrical pulses in cables because light would be immune to the electrical interference common in capacitive touch systems.

New Method for Making Neurons Could Lead to Parkinson's Treatment

Revamping the brain: Human dopamine-producing cells (marked in red and green) survive and function when transplanted into the brain of rats with brain damage that resembles Parkinson’s disease.
Nature

BIOMEDICINE

New Method for Making Neurons Could Lead to Parkinson's Treatment

When transplanted into rodents with brain damage similar to Parkinson's, the cells reversed the animals' motor issues.

• MONDAY, NOVEMBER 7, 2011
• BY EMILY SINGER

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A new method of synthesizing dopamine-producing neurons, the predominant type of brain cell destroyed in Parkinson's, offers hope for creating cell-replacement therapies that reverse the damage.

The method provides an efficient way of making functional cells. When transplanted into mice and rats with brain damage and movement problems similar to Parkinson's, the cells integrated into the brain and worked normally, reversing the animals' motor issues.

The finding brings researchers a step closer to testing a stem-cell-derived therapy in patients with this disorder. "We finally have a cell that seems to survive and function and a cell source that we can easily scale up," says Lorenz Studer, a researcher at the Sloan Kettering Institute and senior author on the new study. "That makes us optimistic that this could potentially be used in patients in the future."

The research also highlights the challenges of generating cells for tissue-replacement therapy, showing that subtle differences in the way the cells are made can have a huge impact on how well they work once implanted.

Many of the symptoms of Parkinson's disease—which include tremor, muscle rigidity, and loss of balance—are linked to loss of dopamine in the brain. While medications exist to replace some of the lost chemical, they do not alleviate all of the symptoms and can lose their effectiveness over time. Scientists hope that replacing lost cells with new ones will provide a more complete and long-term solution.

In the new study, researchers started with human embryonic stem cells, which by definition can differentiate into any cell type. To make a specific type of cell in high numbers, scientists expose the stem cells to a cocktail of chemicals that mimic what they would experience during normal development.

While stem-cell researchers had previously been able to create dopamine-producing neurons from human stem cells, these cells did little to alleviate movement problems in animals engineered to mimic the symptoms of Parkinson's. In 2009, Studer and others developed a method of making the cells that more closely mimics the way they form during development. The resulting cells also carry more of the molecular markers that characterize dopamine-producing cells in the brain.

Light-Based Therapy Destroys Cancer Cells

Light touch: Researchers treated the tumor on the right-hand side of this mouse’s body with a light-activated therapy. The top image is before treatment; the bottom is after.
Hisataka Kobayashi, National Cancer Institute

BIOMEDICINE

Light-Based Therapy Destroys Cancer Cells

The new approach, which features a heat-sensitive fluorescent dye, could eventually replace standard chemotherapy.

• TUESDAY, NOVEMBER 8, 2011
• BY ERICA WESTLY

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For more than two decades, researchers have tried to develop a light-activated cancer therapy that could replace standard chemotherapy, which is effective but causes serious negative side effects. Despite those efforts, they've struggled to come up with a light-activated approach that would target only cancer cells.

Now scientists at the National Cancer Institute have developed a possible solution that involves pairing cancer-specific antibodies with a heat-sensitive fluorescent dye. The dye is nontoxic on its own, but when it comes into contact with near-infrared light, it heats up and essentially burns a small hole in the cell membrane it has attached to, killing the cell.

To target the tumor cells, the researchers used antibodies that bind to proteins that are overexpressed in cancer cells. "Normal cells may have a hundred copies of these antibodies, but cancer cells have millions of copies. That's a big difference," says Hisataka Kobayashi, a molecular imaging researcher at the National Cancer Institute and the lead author of the new study, published this week in Nature Medicine. The result is that only cancer cells are vulnerable to the light-activated cascade.

The researchers tested the new treatment in mice and found that it reduced tumor growth and prolonged survival.

There are a few kinks to work out before the system can be adapted for humans, though. For instance, the researchers couldn't test the treatment's effect on large tumors, since killing off too many cells at once caused cardiovascular problems in the mice. Finding the right cancer-cell markers to pair with the dye may also prove difficult. For example, HER-2, one of the proteins targeted in the study, is only expressed in 40 percent of breast-cancer cells in humans.

Still, the lack of toxicity associated with the treatment is a huge advantage, says Karen Brewer, a chemist at Virginia Tech who also works on light-activated cancer therapies. "What's interesting about this study is that they're applying a traditional method of targeting cancer cells to a light-activated treatment," she says. "This is really where the field is headed."

The dye used in the study offers another bonus because it lights up—allowing clinicians to track the treatment's progress with fluorescence imaging. In the mice, the fluorescence visibly declined in tumor cells a day after administration of the near-infrared light. Kobayashi suspects the approach could also prove valuable as a secondary therapy by helping surgeons label cancer cells that may remain after a tumor has been excised. "It could help clean up the tumor cells that are harder for surgeons to get to," he says.