Nerve repair, biodetectors, proton therapy, microscopic medical devices

Biomedical research highlights of AVS 55th International Symposium & Exhibition in Boston, Oct. 19-24


Despite the success of organ transplantation surgery, many people in need of transplants die while on the waiting list because of the scarcity of donated organs. Artificial, lab-grown organs offer one potential solution to the problem. One novel engineering technique involves the use of modified thermal ink-jet printers to “print” cells, creating the complex three-dimensional structure of real tissues. A lingering question, however, is how well cells survive the process.

Bioengineering graduate student Xiaofeng Cui of Clemson University tested this with a comprehensive study of changes in heat shock protein expression and the morphology of cells after printing. Heat shock protein expression is elevated in response to cell heating and stress. Cui and colleagues found only minor changes in heat shock protein expression after the printing process compared to unprinted cells. They also discovered an interesting side-effect from the process: the creation of small, temporary membrane pores in the printed cells, which could be used for the targeted delivery of drugs and plasmid transfer. “The survival rate of printed mammalian cells is higher than 90 percent, which means the printed cells can repair these changes caused during the printing,” Cui says.

Cui’s talk, “Heat Shock Protein Expression and Cell Membrane Study of Printed Chinese Hamster Ovary Cells,” is at 9:00 am on Tuesday, October 21, 2008, in Room 202 of the Hynes Convention Center. Abstract: . IMAGE AVAILABLE — SEE BELOW.


Over the last 10 years, researchers and clinicians have begun to use microelectromechanical systems (MEMS), which combine electronics technology with tiny mechanical devices like sensors and valves embedded in semiconductor chips–in the biomedical laboratory, to help automate diagnostic testing procedures. The next step, according to Shuvo Roy and other MEMS researchers, is moving MEMS into the body as the basis for implantable drug delivery devices, imaging systems, surgical tools, and more.

“MEMS technology promises to revolutionize medicine by enabling the development of miniature, smart, low-cost biomedical devices that can revolutionize biomedical investigation and clinical practice,” says Roy, an associate professor of bioengineering at the University of California, San Francisco.

For example, Roy and his colleagues are now designing membranes that would allow dialysis to be miniaturized into implantable devices, freeing kidney failure patients from the cumbersome process, and have created wireless sensors for orthopedics that could monitor the need for spine surgery, bone healing, and implant performance.

Roy will discuss these developments and the future of bioMEMS technology in his talk, “MEMS for Implantable Medical Devices,” at 4:40 p.m. on Tuesday, October 21, 2008, in Room 309 of the Hynes Convention Center.


Spinal cord injuries are often a worst-case diagnosis for people who suffer accidents because they may mean permanent Disability. Unlike a broken leg or pulled muscle, spinal cord injuries do not heal themselves over time.

One of the great hopes of modern medicine is that science, particularly the field of biomedical engineering, will someday help heal spinal cord injuries by guiding and stimulating the regenerating neurons to replace the lost connections. But regenerating neurons is not enough. The neurons must also get wired up correctly. They may not be able to do this on their own, however, because the scar tissue formed where the spinal injury occurs may be thick and impossible for neurons to grow across.

Now Thomas P Beebe, Jr. and his colleagues at the University of Delaware have developed a technology for patterning molecules on a surface in a way that can help guide the growth of new neurons. Naturally developing neurons use such patterns much like cars use GPS or global positioning systems to help guide them in the right direction as they grow. Beebe and his colleagues have made their patterned surfaces on glass and polymer surfaces, and they can watch neurons grow on these slides under the microscope. Right now, they are trying to find the optimal conditions that will help the neurons grow across the slide.

“Understanding what causes the neurons to grow fast, to turn around and grow the other way, or not to grow at all, is the first step in the eventual design of a new Biotechnology aimed at spinal cord injuries,” said Beebe. “This is promising, but we are years away from helping people to walk again.”

The idea is to use this basic neuronal technology to develop a healing scaffold-a device made of pliable mesh, porous gels, or some other implantable material that can be used to regenerate spinal cords. Application of this technology may also someday help in the treatment of neurodegenerative diseases in the brain and spinal cord. This technology, however, is not tested in the clinic, and it would have to prove to be safe and effective in clinical trials before becoming widely available.

Beebe’s talk, “Patterned Protein Gradients of Extracellular Matrix Protein Affect Cell Attachment and Axonal Outgrowth” will be at 5:20 p.m. on Tuesday October 21, 2008, in Room 202 of the Hynes Convention Center.


Injuries to the peripheral nerves-those linking the Central Nervous System to the arms and legs of the body-lead to a loss of sensation and function in 1 in 1000 people. Unlike the nerves of the central nervous system, peripheral nerves can be repaired and regenerated, but this process is often incomplete and ineffective.

To improve the odds, researchers have developed so-called nerve guidance conduits, which are essentially cylindrical tubes surgically implanted between two parts of an injured nerve, providing a guide through which new nerves can grow. But that design is too simple, argues cell biologist John Haycock, a senior lecturer at the University of Sheffield in England, who has built a better NGC. Haycock’s model consists of a scaffold made of thousands of aligned polymer microfibers, each just 5 to 10 millionths of a meter in diameter and 10 to 80 millimeters long. Microchannels created by the fibers provide an intricate scaffold for introducing nerve cells. Tests in the laboratory in which nerve cells were seeded onto the new NGC microfibres show a high degree of cell viability and alignment, which is crucial for the accurate regrowth of nerve fibers.

Haycock’s talk, “Use of Aligned Polymer Microfibres for Peripheral Nerve Repair,” is at 4:40 pm on Tuesday, October 21, 2008, in Room 202 of the Hynes Convention Center.


Despite the fact that proton therapy has been around for years, it is still a relatively uncommon way to treat cancer. Currently there are only five operating proton therapy clinics in the United States — one each in Boston, MA; Loma Linda, CA; Bloomington, IN; Houston, TX; and Jacksonville, FL. To date, fewer than 20,000Americans have been treated with protons (particles found in the nuclei of atoms) in these five facilities. Far more are treated every year with other techniques, such as x-ray radiation.

Where proton therapy is uncommon, however, it is also uncommonly good. Protons give the most conformal dose, meaning that the beam can be carefully shaped to match the outlines of the tumor, minimizing the risk to the surrounding healthy tissue. Still, for years proton therapy has been primarily reserved for treating some of the most complicated cancers, such as those in the head or neck, because it is extremely reliable at removing hard-to-reach tumors growing on highly sensitive tissues like the brain or spine.

Now proton therapy is entering a new phase, says Jay Flanz of Massachusetts General Hospital and Harvard University. At the conference, he will discuss how the type of cancers that are being treated with proton therapy has expanded as the underlying technology has improved. He will also discuss a looming increase in the number of therapy centers. There are as many facilities under construction today as there are currently operating, he says. Part of the reason for this increase is that proton therapy centers require large facilities equipped with particle accelerators. These facilities may cost $100 million or more to build. But where once this equipment had to be fabricated piece-by-piece, there are now commercial companies that can produce brand-new facilities from the ground up.

Flanz’s talk, “Proton Cancer Therapy” is at 2:20 p.m. on Tuesday October 21, 2008, in Room 312 of the Hynes Convention Center.


Hepatitis C affects around 150 million people worldwide and is a major cause of chronic liver disease. Current treatment involves the anti-viral drugs interferon and ribavirin, both of which have serious side effects. As part of ongoing research to combat the hepatitis C virus, researchers are studying how the virus’ replication machinery attaches to cell membranes.

Membrane attachment is a necessary step in the replication of the hepatitis C virus. If doctors can prevent the virus from latching onto membranes inside the host cell, they may be able to control the disease. Curt Frank and Jeffrey Glenn of Stanford University and their colleagues have identified a helical portion of one viral protein, called NS5A, which seems to be one of the virus’ membrane “adhesives.” To understand how this protein works, the scientists exposed the protein to a range of artificial membranes placed on a quartz crystal microbalance. This dime-sized device, which can measure a mass increase of as little as 18 nanograms, recorded how much, if any, of the protein attached to the different membrane surfaces. The team discovered that the protein targets a particular combination of lipid and proteins in cell membranes. With further research, they hope to better pinpoint where the virus latches on, so that drugs might be developed to interfere with the process.

Please note that this presentation Frank’s talk, “Interaction of AH Amphipathic Peptide with Lipid Bilayers and Application to the Understanding of Hepatitis C Viral Infection via QCM-D Measurements” will be part of an honorary session devoted to surface scientist Bengt Kasemo, who has been instrumental in developing the QCM technique. It will be at 2:40 p.m. on Monday October 20, 2008, in Room 202 of the Hynes Convention Center.


Life, on the microscopic level, is crowded and bustling. Tissues are made of cells glommed together that are covered with molecules. The molecules are constantly interacting with other molecules, and how they interact can mean the difference between good health and disease or life and death.

Some of the greatest insights biologists have come from teasing apart the tiny interactions that underlie it all. Now Gil Lee and colleagues at University College in Dublin, Ireland have developed a new way to tweeze apart interacting cells and molecules using magnetic forces. This technology, which relies on attaching microscopic magnetic particles, allows them to measure exactly how strongly the interactions are between biological molecules. They can do this sensitively enough to be able to measure the “bond strength” with which two individual molecules are held together. Bond strength is one of the most important features of molecular interactions because it determines how strongly or weakly molecules in the human body interact-or if they interact at all.

Recently Lee and his colleagues looked at one of the classic pairs of interacting molecules, the protein immunoglobin G, which plays a critical role in the immune system by recognizing pieces of foreign pathogens. Interestingly they saw two types of bonds. One was strong while the other much weaker. They are now expanding this work to look at whole cells and developing the technology as a way to screen particles.

“Magnetic Tweezers Measurement of the Bond Lifetime-Force Behavior of the IgG-Protein A Specific Molecular Interaction” will be at 9:00 a.m. on Wednesday October 22, 2008, in Room 202 of the Hynes Convention Center.


Even very small numbers of deadly infectious agents or allergenic pollen molecules can cause big problems for humans. But detecting such trace amounts is difficult to do fast enough to do any good. Current techniques — for example, air sampling on filters or slides until enough molecules for a detectible signal or preparing specially tagged molecules for lab experiments — are more suitable for general research than alerting people to an imminent threat.

Andrea Armani of the University of Southern California has adapted a clever optical microcavity resonance technique for rapidly detecting even individual unlabelled target molecules. The central element is a microtoroid resonator — a ring of glass about 3 microns thick with a diameter of 100 microns (about the diameter of a human hair). The resonator is created using photolithography techniques developed for the semiconductor industry, but then Armani coats it with a protein that binds only to the target molecule. Finally, a tapered optical fiber is mated tangentially to the ring, enabling tunable laser light to be introduced into the ring so the waves match precisely with each circuit. Should even a single target molecule bind on the outside of the resonator, it will absorb a small amount of light from the “evanescent” field that extends a fraction of a micron beyond the glass ring, causing a change in resonance. Because the light continues to circulate through the ring, even the slight change due to a single molecule is strongly reinforced and can be detected.

Armani will report her successful detection of two Timothy grass pollen proteins, which are major human allergens. Her future efforts aim to adapt this technique to enable the rapid, remote detection of a wide variety of single molecules in the Environment and in vitro.

Armani’s talk, ” Biophotonics: Resonant Detection of Single Molecules” is at 10:40 a.m. on Wednesday, October 22, 2008, in Room 202 of the Hynes Convention Center.

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