Frigital Records

Magnetic nanoparticles coated with a specialized targeting molecule were able to latch on to cancer cells in mice and drag them out of the body. The results are described in a study published online this month in the Journal of the American Chemical Society. The study’s authors, researchers at Georgia Institute of Technology, hope that the new technique will one day provide a way to test for–and potentially even treat–metastatic ovarian cancer.

“It’s a fairly novel approach, to use magnetic particles in vivo to try to sequester cancer cells,” says Michael King, an associate professor of biomedical engineering at Cornell University, who was not involved in the study.

With ovarian cancer, metastasis occurs when cells slough off the primary tumor and float free in the abdominal cavity. If researchers could use the magnetic nanoparticles to trap drifting cancer cells and pull them out of the abdominal fluid, they could predict and perhaps prevent metastasis. Although the nanoparticles were tested inside the bodies of mice, the authors envision an external device that would remove a patient’s abdominal fluid, magnetically filter out the cancer cells, and then return the fluid to the body. After surgery to remove the primary tumor, a patient would undergo the treatment to remove any straggling cancer cells. The researchers are currently developing such a filter and testing it on abdominal fluid from human cancer patients.

“It’s possible that the particles may not ever have to go into the patient’s body,” says John McDonald, chief scientific officer of the Ovarian Cancer Institute at Georgia Tech and a senior author of the paper. “That would be preferable, because then you don’t have to worry about any potential toxicity.”

The particles, which are just 10 nanometers or less in diameter, have cobalt-spiked magnetite at their core. Most of the time they are not magnetic, but when a magnet is present, they become strongly attracted to it. On the surface of the particles is a peptide–a small, proteinlike molecule–designed to attach to a marker that protrudes from most ovarian cancer cells.

To test the new technology, the researchers injected first cancer cells and then the magnetic nanoparticles into the abdominal cavities of mice. The cancer cells were tagged with a green fluorescent marker, and the nanoparticles with a red one. When the team brought a magnet near each mouse’s belly, a concentrated area of green and red glow appeared just under the skin, indicating that the nanoparticles had latched on to the cancer cells and dragged them toward the magnet.

While this experiment showed that the nanoparticles could snag at least some cancer cells within the body, it’s not yet clear what proportion of cancer cells were captured and removed. Tests to pinpoint that proportion are planned.

Cornell’s King suspects that the technology may be better suited to diagnosing, rather than treating, metastasis. “I think that this technology has much more potential for diagnostics and for detecting cancer cells,” he says. “I’m not fully convinced that it could be used to really significantly filter out cancer cells as a therapy.”

A similar technology that uses antibody-coated beads to separate out cancer cells has already proved effective in vitro, but the new study’s authors believe that the magnetic nanoparticles will be less likely to cause an unwanted immune response and are thus better suited for use inside the body. And because they seem to bind more strongly than antibodies to their targets, says McDonald, they may be better able to pull out cancer cells.

“The ideal would be to try to get everything, but I doubt that would happen,” says McDonald. “But we believe that we could significantly reduce the number and thus lower the probability of metastasis.”

For now, the treatment seems uniquely suited to ovarian cancer; most other tumors metastasize through cells floating in the bloodstream rather than in the abdominal fluid. But eventually, the team hopes to adapt the particles for use in blood, perhaps extending their use not only to other cancer types, but also to viral diseases such as HIV. To do so, say the researchers, they will need to develop highly specific targeting molecules for each disease to ensure that healthy blood cells are spared.

To test the feasibility of using the nanoparticles in the bloodstream, Ken Scarberry, a graduate student at Georgia Tech and coauthor of the study, reports watching them in action in an artificial circulatory system that passed under a fluorescent microscope. When a magnet was placed near the microscope’s lens, “you could see that all of the cells immediately got sequestered over to the side and did not move as the fluid continued to flow,” says Scarberry. “This technology has so many possibilities. Right now, I think we’re just scratching the surface with it.”

Source:www.technologyreview.com

The “ECG-on-a-chip” solution combines Monebo’s Kinetic ECG software with Freescale’s embedded processing technology to enable medical equipment manufacturers to develop easy-to-use ECG monitoring tools.

According to the World Health Organization (WHO), cardiovascular disease is the leading cause of death globally. An estimated 17.5 million people died from cardiovascular disease in 2005, representing 30 percent of all global deaths. Of these deaths, 7.6 million were due to heart attacks and 5.7 million were due to stroke. By 2015, an estimated 20 million people will die from cardiovascular disease every year, primarily from heart attacks and strokes.

Many of these deaths will occur with no previous symptoms of cardiovascular disease. ECG monitors are vital tools used by healthcare providers to identify cardiac conditions and monitor a patient’s health.

“Individuals affected by many forms of cardiovascular disease often go untreated, as they’re either unaware they have the condition, or have misgivings about traditional treatments available,” said Dr. Jose Fernandez Villasenor, global medical applications specialist at Freescale Semiconductor. “Breakthrough silicon and software technologies from companies like Freescale and Monebo are making it easier and more cost-effective to monitor heart patients using a critical and widely understood test, the ECG.”

To help health care professionals assess cardiac parameters, Monebo Technologies has developed the Kinetic ECG algorithm, which enables signal processing and interpretation of the ECG waveform. The algorithm provides highly accurate QRS (Q wave, R wave and S wave) detection and feature extraction, beat classification, interval measurement and rhythm interpretation for up to 16 leads of captured ECG data.

Monebo’s Kinetic software is designed to run on a broad range of Freescale processors and microcontrollers (MCUs). This versatile choice of processing platforms gives developers tremendous freedom of choice in addressing their ECG application needs, based on performance, operating power, integration and system cost.

“Based on our unique software algorithms and Freescale’s processing platforms, we have the technology to provide detailed information to the clinician, enabling physicians to monitor heart patients from a remote location, and also analyze and interpret ECG data from any device, including those used for pharmaceutical clinical trials,” said Dale Misczynski, president and CEO, Monebo Technologies.

Faster time to market for medical device designers

Today’s medical device designers face the challenge of creating increasingly more complex products and bringing these products to market faster. The pairing of the Kinetic algorithm with Freescale MCUs enables designers to add advanced ECG monitoring functionality and get to market fast.

Freescale’s embedded processors and MCUs contain the necessary integration to add innovative technology to next-generation medical devices, and the US Food and Drug Administration (FDA) 510(k) clearance on the Kinetic algorithm streamlines end-device regulatory filings.

The Monebo software can be combined with key products in Freescale’s MCU and embedded processor portfolio, including HCS08, ColdFire, PowerQUICC, i.MX, digital signal controller (DSC) devices. The overall benefits of this combined hardware/software solution include:

* Faster time-to-market: By streamlining FDA validation and reducing development time.
* Scalability: Medical device designers can develop optimal designs based on the unique capabilities of Freescale embedded processors and Monebo software.
* Lower development costs: The ECG-on-a-chip solution is thoroughly tested and validated and provides a “one-stop shop” approach for medical designers.

“Freescale believes consumers can monitor their health more effectively if they have access to medical devices that are embedded into their daily lives,” said Henri Richard, senior vice president, chief sales and marketing officer, Freescale. “Freescale technology helps broaden the ECG medical device market by speeding time-to-market, offering best-in-class hardware and software, and reducing system cost. Ultimately, ECG-on-a-chip solutions will result in new generations of ECG products designed to help improve the quality of life for millions of people affected by cardiovascular disease.”

The ECG-on-a-chip solution is ideal for a wide spectrum of applied technology, such as:

* Event recording: auto-trigger alarms to warn of heart problems and call center decision support.
* Bedside patient monitoring: real-time monitoring of patients with instant access to information by doctors.
* Pharma: interval measurements for clinical trials or monitoring and adjusting patient dosage of medicine.
* Monitors to aid in cardiac rehabilitation.
* Home medical: portable devices to monitor patients from home.
* Health and fitness: equipment to monitor heart health and optimize workouts.

Physicians often test the levels of a few telltale blood proteins in seriously injured or ill patients to detect organ failure and other problems. Now Vista Therapeutics, a startup based in Santa Fe, NM, hopes to improve the care of these patients with sensitive devices for continuous bedside monitoring of such blood biomarkers. Instead of taking daily snapshots of the patient’s levels of blood proteins, the company’s nanosensors should allow for continuous monitoring of changes that occur over periods of only a few hours.

Spencer Farr, CEO of Vista Therapeutics, says that the first application of the technology will be for careful monitoring of patients whose status can change rapidly–such as those in the ICU after suffering a heart attack or traumatic injuries from a car accident. “We envision having a branch in the patient’s IV that tests continuously or every five to ten minutes,” says Farr. The nanowires are sensitive enough that they should be able to detect trace biomarkers that diffuse into the IV line from the blood. After a car wreck, for example, patients could be closely monitored for molecular warning signs of impending kidney and other organ failure.

To make the detectors, Vista Therapeutics has licensed nanowire sensing technologies developed by Harvard University chemist Charles Lieber. Silicon nanowires, semiconducting wires as thin as two nanometers, have what Lieber calls the “ultimate sensitivity,” even with completely unprocessed samples such as blood. When a single protein binds to an antibody along the wire, the current flowing through the wire changes. Arrays of hundreds of nanowires, each designed to detect a different molecule in the same sample, can be arranged on tiny, inexpensive chips. The changes can be monitored continuously as molecules bind and unbind, making it possible to detect subtle trends over time, without requiring multiple blood draws.

The standard protein-detection technique, ELISA, is very sensitive but, Farr says, takes 90 minutes to perform. It starts with a blood draw that must be extensively processed–first to purify the proteins, then to label them with fluorescent dyes–and then tested with expensive imaging equipment in a hospital lab. “ELISA is a powerful technology for one-time measurements,” says Farr, “but there’s no existing technology for continuous biomarker measurement.”

The sensitivity of nanowire detectors should also open up the possibility of finding new biomarkers. The blood biomarkers that doctors routinely test for–including prostate-specific antigen for cancer screening and c-reactive protein, a sign of heart failure–can be monitored with ELISA because their levels change over days or weeks. Because nanowire sensors allow for extremely sensitive, continuous monitoring, they should allow doctors to monitor the levels of blood proteins and other molecules whose concentration changes over a much shorter timescale. Changes in these biomarkers are currently undetectable. “We expect we’ll be able to include those that change rapidly, peaking within a matter of a few hours,” says Farr. Because it hasn’t been practical to make such measurements before, it’s not clear just what these biomarkers will be, but Farr hopes that Vista will uncover them.

Initially, Vista will market clinical devices for monitoring known biomarkers in IV lines. In the future, the company might develop implantable chips for patients with chronic diseases such as diabetes. A nanowire chip in an artery in the wrist might continuously monitor blood glucose and proteins indicative of early liver damage and other diabetic complications. The device could send alerts to a wristwatch. Because nanowires are so sensitive and inexpensive, they could also find their way into home tests for cancer, where early detection is key, says Farr.

Around the time that the swimwear company Speedo was calling on NASA scientists to help create the now famous LZR Racer suit–an enhanced skin that many people credit for more than a dozen world records broken by swimmers so far this week in Beijing–a scientist in New York began working on a different tool for the swimmer’s armory. Over the past five years, Tim Wei, a mechanical and aerospace engineer at Rensselaer Polytechnic Institute, has revamped an established technique in fluid dynamics to study human movement for the first time. The method allows scientists and coaches to study how fast and hard a swimmer pushes the water as she moves through it. Swim coach Sean Hutchison, who put two athletes on the Olympic swim team, says that he used Wei’s insights as the basis for every technical change he made with swimmers leading up to the Olympic trials and games this year.

Wei uses a tracking technique called digital particle image velocimetry, commonly used to measure the flow of small particles around an airplane or small fish or crustaceans in water. For water-based flow experiments, researchers pour minute silver-coated beads into water and illuminate them with a laser. A high-speed digital video camera tracks the downstream flow of beads over the creature. “But ramping up to large scales is hard,” says biologist Frank Fish, who studies the propulsion of aquatic mammals at West Chester University and has collaborated with Wei on dolphin studies. “Shining lasers on swimmers and immersing them in water full of glass beads may be asking them to go above and beyond in the name of science.”

Wei devised a novel solution: instead of glass beads, he filtered compressed air in a scuba tank through a porous hose to create bubbles about a tenth of a millimeter in diameter. An athlete swims through a sheet of bubbles that rises from the pool floor, and a camera captures their flow around the swimmer’s body. Images show the direction and speed of the bubbles, which Wei then translates into the swimmer’s thrust using software that he wrote. “More force equals faster swimming,” he says.

“[Hutchison] took that and modified the breaststroke kick of all his elite athletes,” says Wei, who presented his work to USA Swimming, the sport’s governing body, in 2007. In a sport in which shaving tenths of a second can be cause for celebration, Hutchison reported that by adapting her kick, Kukors dropped several seconds in a breaststroke event, although she just missed the Olympic team. Jendrick and another of Hutchison’s swimmers, Margaret Hoelzer, are competing this week at the games, where Jendrick placed fifth in the 100-meter breaststroke and Hoelzer, who won a bronze in the 100-meter backstroke, hopes to win gold in the 200 back. She broke the world record in the event in July.

More recently, Wei has turned his attention to a swimmer’s thrust. With funding from USA Swimming, Wei built a force balance, an upside-down triangular frame that acts like a bathroom scale. Swimmers lie outstretched in the water and kick into the frame, and it measures their propulsion over time. The output, which for an elite swimmer like Kukors showed a sinusoidal, repetitive wave, can help coaches determine whether an athlete should try to generate more force with a harder, bigger kick rather than a shallower, quicker one. “It depends on the individual swimmer,” says Wei, who hopes to combine flow and thrust measuring tools into one image. He also wants to make more measurements of athletes swimming freely, rather than pushing against a wall or in a flume.

Wei will meet with USA Swimming biomechanics coordinator Russell Mark in the fall to talk about what to do next. “Russell’s job is providing coaches with a sound physics base for whatever they tell swimmers to do,” Wei says. USA Swimming also relies on computer-based flow analysis using whole-body scans of swimmers; these could be combined to determine how one validates the other.

Source:www.technologyreview.com