College of Engineering Magazine- Fall 2001

ENG Research Briefs

by Joan Schwartz

In Nano-focus

Selim Unlu, an ENG associate professor of electrical and computer engineering, Bennett Goldberg, a CAS associate professor of physics, and electrical engineering doctoral candidate Stephen Ippolito ('02) have developed a novel subsurface microscope that can focus on the minute structural detail of silicon-based integrated circuits - a tool with enormous potential for ensuring the quality of these tiny devices that are the building blocks of our information-age technology.

Silicon integrated circuits are difficult to image. The fronts of integrated circuit silicon wafers are typically covered with opaque metal layers, making it necessary to image them from the back, which is transparent to light at infrared wavelengths. Since ordinary microscopes are limited by diffraction to a resolution of half the wavelength of light (0.5 micrometers), they are much too coarse for the intricate lithographed features of the integrated circuits in use today, which can be as small as 0.13 micrometers.

The researchers increased the resolution of the microscope by pairing it with a numerical-aperture-increasing lens, or NAIL. The NAIL is made of the same material as the sample and both are polished to achieve optimum contact and avoid surface reflection. The dome-shaped NAIL is constructed so that the radius of its curved surface and the distance from the surface of the dome to the object allow undistorted imaging. The NAIL allows light once reflected by the surface of the wafer to travel into the lens of a traditional microscope system.

The researchers have been able to produce images with a resolution of 0.23 micrometers, and expect to refine the device further to improve resolution to less than 0.2 micrometers. See http://ultra.bu.edu/projpages/nail.

Contact Point

On a cellular level, biological processes begin with binding. Before a substance, whether a manufactured pharmaceutical or the body's own antibodies, can enter a cell, it must find a firm footing to adhere to the cell surface. This is accomplished by ligands, protein molecules tethered to the outside of a cell that are specifically designed to fit into surface receptors on the target cells. Ligand-receptor pairs are as specific to each other as a lock and key.

Joyce Wong, Clare Boothe Luce Assistant Professor of Biomedical Engineering, has been investigating the factors that govern ligand-receptor binding with the aim of creating new systems for more effective, targeted drug delivery. In a series of experiments, Wong and colleagues at the University of California, Santa Barbara, the University of California, Davis, Alza Corporation, and Strasbourg's Centre National de la Recherche Scientifique employed liposomes, artificially created microscopic sacs designed to carry potent drugs to targeted cells, polymer tethers, and a well-documented ligand-receptor pair, biotin-streptavidin.

They revealed that the interplay between the ligand and receptor is not only significant in the overall range, rate, and ultimate strength of the bond formation, but also in the length and dynamics of the tether chain. Wong now plans to test these results in real cells, specifically the Anti-HER2 cells implicated in breast cancer. She is also investigating how other factors, such as the flow rate of blood carrying the therapeutic agents, impact binding. This work is also crucial to the development of other therapeutic modalities, such as the creation of bioengineered tissue.

Muscling in on Asthma

Asthma has been increasing in the United States since the early 1980s, afflicting 14.6 million people in 1998. In 1994 alone, the cost of treating this chronic lung disease was estimated at $10.7 billion. Asthma is one of only three chronic diseases (along with AIDS and tuberculosis) that has an increasing death rate - it now kills fourteen Americans every day. Characterized by inflammation of the air passages and temporary narrowing of the airways to the lungs, asthma is increasingly common in children.

College of Engineering Biomedical Engineering Professor Kenneth Lutchen and graduate student Andrew Jensen ('01) have been working to determine if asthma stems from a defect in the function of the smooth muscle of the airway. They developed a method to monitor in real time the action of airway muscles while patients, both healthy and asthmatic, are breathing. As the researchers reported in the Journal of Applied Physiology this summer, they found that the smooth muscles in the airways of asthmatics are different from those in healthy individuals, constricting with greater force and becoming stiffer when constricted, which prevents the airway from reopening during a deep breath. Lutchen and his colleagues are now investigating the various factors that create the stiffness in the airway muscle. They suspect that it may be related to increased thickness of the muscle and decreased periodic stretching.


ENG Research Briefs by Joan Schwartz In Nano-focus Selim Unlu, an ENG associate professor of electrical and computer engineering, Bennett Goldberg, a CAS associate professor of physics, and electrical engineering doctoral candidate Stephen Ippolito ('02) have developed a novel subsurface microscope that can focus on the minute structural detail of silicon-based integrated circuits - a tool with enormous potential for ensuring the quality of these tiny devices that are the building blocks of our information-age technology. Silicon integrated circuits are difficult to image. The fronts of integrated circuit silicon wafers are typically covered with opaque metal layers, making it necessary to image them from the back, which is transparent to light at infrared wavelengths. Since ordinary microscopes are limited by diffraction to a resolution of half the wavelength of light (0.5 micrometers), they are much too coarse for the intricate lithographed features of the integrated circuits in use today, which can be as small as 0.13 micrometers. The researchers increased the resolution of the microscope by pairing it with a numerical-aperture-increasing lens, or NAIL. The NAIL is made of the same material as the sample and both are polished to achieve optimum contact and avoid surface reflection. The dome-shaped NAIL is constructed so that the radius of its curved surface and the distance from the surface of the dome to the object allow undistorted imaging. The NAIL allows light once reflected by the surface of the wafer to travel into the lens of a traditional microscope system. The researchers have been able to produce images with a resolution of 0.23 micrometers, and expect to refine the device further to improve resolution to less than 0.2 micrometers. See http://ultra.bu.edu/projpages/nail. Contact Point On a cellular level, biological processes begin with binding. Before a substance, whether a manufactured pharmaceutical or the body's own antibodies, can enter a cell, it must find a firm footing to adhere to the cell surface. This is accomplished by ligands, protein molecules tethered to the outside of a cell that are specifically designed to fit into surface receptors on the target cells. Ligand-receptor pairs are as specific to each other as a lock and key. Joyce Wong, Clare Boothe Luce Assistant Professor of Biomedical Engineering, has been investigating the factors that govern ligand-receptor binding with the aim of creating new systems for more effective, targeted drug delivery. In a series of experiments, Wong and colleagues at the University of California, Santa Barbara, the University of California, Davis, Alza Corporation, and Strasbourg's Centre National de la Recherche Scientifique employed liposomes, artificially created microscopic sacs designed to carry potent drugs to targeted cells, polymer tethers, and a well-documented ligand-receptor pair, biotin-streptavidin. They revealed that the interplay between the ligand and receptor is not only significant in the overall range, rate, and ultimate strength of the bond formation, but also in the length and dynamics of the tether chain. Wong now plans to test these results in real cells, specifically the Anti-HER2 cells implicated in breast cancer. She is also investigating how other factors, such as the flow rate of blood carrying the therapeutic agents, impact binding. This work is also crucial to the development of other therapeutic modalities, such as the creation of bioengineered tissue. Muscling in on Asthma Asthma has been increasing in the United States since the early 1980s, afflicting 14.6 million people in 1998. In 1994 alone, the cost of treating this chronic lung disease was estimated at $10.7 billion. Asthma is one of only three chronic diseases (along with AIDS and tuberculosis) that has an increasing death rate - it now kills fourteen Americans every day. Characterized by inflammation of the air passages and temporary narrowing of the airways to the lungs, asthma is increasingly common in children. College of Engineering Biomedical Engineering Professor Kenneth Lutchen and graduate student Andrew Jensen ('01) have been working to determine if asthma stems from a defect in the function of the smooth muscle of the airway. They developed a method to monitor in real time the action of airway muscles while patients, both healthy and asthmatic, are breathing. As the researchers reported in the Journal of Applied Physiology this summer, they found that the smooth muscles in the airways of asthmatics are different from those in healthy individuals, constricting with greater force and becoming stiffer when constricted, which prevents the airway from reopening during a deep breath. Lutchen and his colleagues are now investigating the various factors that create the stiffness in the airway muscle. They suspect that it may be related to increased thickness of the muscle and decreased periodic stretching.
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