Engineering

Photonics Symposium Showcases Innovations in Point-of-Care Diagnostics

Fri, 20 Nov 2009 00:00:00 EST

To better understand, diagnose and treat specific diseases, scientists are increasingly seeking technologies to investigate biological systems at the cellular and molecular levels. Among the most promising is biophotonics, the study of the interaction of light with biological material. Drawing on research in the life sciences, physical sciences and engineering, emerging biophotonics technology is extending scientists’ ability to image, analyze and manipulate living tissue in minimally invasive ways.

On Nov. 16 at the Photonics Center, the 13th annual Future of Light Symposium, “Biophotonics Sensors and Systems: Point of Care Diagnostics,” showcased leading edge research in biophotonic imaging and biomedical photonics. Chaired by Professor Irving Bigio (BME, ECE), the symposium highlighted the achievements of Photonics Center researchers and collaborators from academic and medical institutions in Greater Boston and across the country.

Contributing to three separate technical sessions of the conference, three College of Engineering faculty members — Professor Selim Ünlü (BME, ECE), Associate Professor Jerome Mertz (BME) and Assistant Professor Satish Singh (BME) — presented new methods that could improve the accuracy, efficiency and cost-effectiveness of point-of-care diagnostic tools.

Mertz described HiLo microscopy, a new imaging technique that could be used in endoscopic microscopes. Rather than requiring researchers and clinicians to extract and bring tissue to the microscope, endomicroscopy enables them to bring the microscope to the tissue. HiLo microscopy produces a three-dimensional image of a tissue sample based on an inexpensive modification to a wide-field fluorescence microscope.

Fusing low-resolution data obtained from a non-uniformly illuminated image — one generated by illuminating the tissue sample with a grid-based or other pattern of light — with high-resolution data from a uniformly illuminated image, the method yields a high-contrast, in-focus image.

“It’s very simple, there are no moving parts, it’s very fast, there are reduced motion artifacts, and it’s very insensitive to the type of structural illumination used,” noted Mertz, whose lab is seeking to implement HiLo microscopy in a clinically useful endoscope to facilitate early cancer detection in the colon and other tissues.

Singh, a staff gastroenterologist at the Veterans Administration Boston Healthcare System, introduced a promising new fiber optic probe that he’s devised that could considerably improve the effectiveness of traditional colonoscopy. Incorporating optical spectroscopic imaging into a conventional colonoscopic forcep, the probe performs an optical biopsy in concert with the physical biopsy of the colon.

“The analysis to date reveals great promise for the system to classify colonic polyps in situ,” said Singh, citing a study that he and colleagues conducted at the Boston VA. “The system has the potential to be a low cost, low maintenance, user-friendly, easily adopted clinical tool.”

Ünlü discussed the development of a simple technique — the Spectral Reflectance Imaging Biosensor (SRIB) — based on the interference of light reflected from a silicon dioxide surface. Measuring optical path length differences caused by biomolecular binding on the surface, the SRIB could be used to detect proteins, DNA and single viruses.

“We can get not only multiplexed, label-free results, but we can also do dynamic measurements,” said Ünlü, who has already commercialized the high-throughput technique and applied it to the study of liver and Alzheimer’s diseases.

Nanophotonics Advance Could Boost Biomolecular Studies and Sensor Capabilities

Fri, 30 Oct 2009 00:00:00 EDT

An interdisciplinary team of researchers led by Assistant Professor Hatice Altug (ECE) has created a highly sensitive, infrared (IR) absorption spectroscopy technique that can identify specific proteins and other molecules using far less sample material than what conventional spectrometers require. Exploiting recent advances in nanophotonics, the technique constitutes a powerful new tool for biomolecular studies and drug discovery, and could considerably enhance biological and chemical sensor detection capabilities.

Infrared absorption spectroscopy uses infrared light to excite the bonds that connect atoms within molecules, causing them to vibrate at a specific resonant frequency. By examining what frequencies of light are absorbed by a material, scientists can determine what kind of bonds it contains, and thus identify the material.

Because absorption signals are often weak, conventional IR spectroscopy requires large samples of target molecules in many layers. To overcome this limitation, the research team used tiny gold nanoparticles as highly efficient “nanoplasmonic” antennas that greatly amplify the signal received from an individual protein molecule.

“Our technique enhances the signal by a factor of up to 100,000,” said Altug. “Because our technique is ultra-sensitive, we don’t need a large number of molecules from which to obtain signals. In fact, we can obtain signals from even a single-molecule-layer thick protein film.”

Altug and her collaborators — Professor Shyamsunder Erramilli (BME, Physics); Research Professor Mi Hong (Physics); graduate student Ronen Adato and post-doctoral fellow Ahmet Ali Yanik in Altug’s lab; and Tufts University bioengineers David Kaplan, Fiorenzo Omenetto and Jason Amsden — report on this unprecedented achievement in this week’s online edition of Proceedings of the National Academy of Sciences.

Nanoantennas Dramatically Improve Detection Capability
To obtain the high sensitivity needed to detect vibrations from an extremely small sample of silk protein molecules, the team designed a 50-by-50 array of gold, rod-shaped nanoantennas and tuned their resonant frequency to match that of the bonds within the sampled molecules.

The 2,500 strategically configured antennas focus infrared light on nearly 145 silk protein molecules deployed at the tip of each nanoantenna. The light, in turn, excites the bonds within the molecules to vibrate at their signature 6.6 micron wavelength. After absorbing a significant fraction of the incoming IR light, the silk protein molecules reflect the rest back through the nanoantennas. Upon receipt of the reflected signal, the spectrometer deduces the vibrational signature of the silk protein molecules.

Combining theoretical calculations and advanced nanofabrication techniques, Yanik and Adato obtained up to a 100,000-fold enhancement of the molecules’ vibrational signatures and whittled the sample thickness down to a single layer of protein.

Drawing on seed funding from an ENG Dean’s Catalyst Award and ongoing support from the National Science Foundation, Massachusetts Life Science Center and Department of Defense, Altug and her co-investigators are now applying their novel IR spectroscopy technique to other kinds of molecules.

“Our plasmonic method is quite general and can be adapted to enhance the infrared fingerprints of other biomolecules, such as nucleic acids and lipids,” said Altug. “It therefore provides a general purpose toolkit for ultra-sensitive vibrational spectroscopy of biomolecular systems.”

Drug Discovery Implications
Because the technique requires only one-layer, two-nanometer-thick samples, it may ultimately enable scientists to obtain much more accurate and useful data.

“The sensitivity of our technique can be high enough to provide spectroscopy at the single-molecule scale,” said Altug, “and a single-molecule response can be very different from that of an ensemble of molecules.”

Studying protein molecules in one layer offers yet another advantage.

“Conventional IR spectroscopy requires a large number of proteins, usually 5,000 to 10,000 layers of them in one stack that resembles a baklava,” said Erramilli. “With our single-layer substrate we can capture proteins in their native environment.”

As a result, the new technique could be used to improve our understanding of how protein molecules interact and how external forces alter their shape and behavior — questions of fundamental importance in biochemistry and drug discovery.

The method may also help amplify biological and chemical sensing capabilities in defense and other applications.

“Chemical sensors detect the presence of specific molecules via molecular fingerprints, telltale vibrational frequencies of the molecules’ bonds,” Altug explained. “Our technique’s ultra-sensitivity enables us to pick up clear, identifiable response signals even from a trace amount of a chemical.”

At Alumni Weekend, Clean Energy a Hot Topic

Wed, 28 Oct 2009 00:00:00 EDT

Members of the College of Engineering community – alumni, faculty, students and staff – gathered on Oct. 23 for the College’s second annual Future of Engineering Symposium, which focused on engineering’s role in clean energy solutions and helped kick off Boston University’s Alumni Weekend.

The symposium, “Amplifying the Societal Impact of Engineering Research: A Case Study in Clean Technology,” was hosted by College of Engineering Dean Kenneth R. Lutchen, and featured a keynote address from Yet-Ming Chiang, Kyocera professor of ceramics in the Department of Materials Science and Engineering at MIT.

“Right now, we’re in a golden age of engineering,” Lutchen said. “We’re facing many problems that need to be solved through engineering. And these problems need an engineering education, which will lead to real-world engineering solutions.”

Chiang’s talk focused on the extensive engineering research in the Boston-Cambridge area, clean energy storage, the critical emergence of the battery industry as long-term energy solution, and the quest for an affordable and clean electric vehicle.

“There’s never been a better time for engineering research to have an impact on technology and society,” Chiang said. “Research breakthroughs are still needed in many areas, but with so many factors – global warming, supply and demand, energy independence – driving our research, we continue to push the envelope to achieve these solutions in the future.”

A founding scientist of American Superconductor, a leading manufacturer of high-temperature, super-conducting wire for energy and power applications, and A123Systems, one of the world's leading suppliers of high-power lithium ion batteries, Chiang’s research in new battery technology earned him a R&D Magazine “R&D 100” and “R&D Editor’s Choice Award” in 2006.

“On a worldwide scale, the battery industry is as small as a lug nut,” Chiang said. “But it’s also critical, because without the lug nut, you lose the wheel. With renewable energy becoming widespread, increased storage will be needed. As an old colleague once said, ‘He who cannot store, will have no power after four.’”

While costs remain prohibitive, Chiang said advances are being made in the field of clean, electric automobiles, which was highlighted by a video demonstration of a “killacycle” electric motorcycle going from zero to 60 miles per hour in under a second. New battery research is playing a critical role, particularly through advancements in nanotechnology and materials science engineering.

“Materials science engineering is critical to the life of the battery, and energizing nanoscale batteries is critical to battery performance,” he said. “New breakthroughs will lead to new models and different ways to look at research. And as research grows, the rate of adoption continues, and engineering metrics continue to advance.”

Following the symposium, clean energy discussions continued throughout alumni weekend. On Oct. 24, Professor Michael Caramanis (ME) co-hosted the alumni college class, “The Future of Clean Energy: Challenges to Sustainable Energy Technology.” The interactive discussion focused on the future of the electric “SmartGrid” and the importance of consumer information in efficiently managing energy consumption.

Also on Oct. 24, Boston University President Robert A. Brown hosted the Inaugural President’s Panel on Energy, which featured a panel of industry experts, including representatives from the U.S. Department of Energy, Massachusetts Department of Energy Resources, and DuPont, Inc., and explored alternative sources for creating ethanol.

BME Researchers Help Advance Novel Personal Genotyping Technique

Tue, 27 Oct 2009 00:00:00 EDT

To determine your personal predisposition to selected diseases, you can send a sample of your own DNA, along with a few hundred dollars, to one of several personal genotyping firms. Using a commercially available gene chip, a technician will then compare specific nucleotides in your DNA sample against hundreds of thousands of catalogued positions in the human genome, and pinpoint locations where the sample departs from the norm — and may indicate disease susceptibility.

Now a novel approach to genotyping that could provide additional personal genetic information has emerged from a team of scientists that includes three researchers in the Biomedical Engineering Department — Michael Molla, a Center for Biodynamics fellow and post-doc in Prof. James Collins’ lab; Simon Kasif, professor of bioinformatics and biomedical engineering and director of the Computational Genomics Lab; and Prof. Charles Cantor of the Center for Advanced Biotechnology. The team reported on its innovation in the October 6 edition of Proceedings of the National Academy of Sciences.

A New Approach to Genotyping
The new genotyping strategy exploits variations in the lengths of short DNA sequences called short tandem repeats (STRs) that appear over and over again in thousands of regions of the human genome. For example, in the short sequence of nucleotide bases “AGCAGCAGCAGCAGC,” the triplet "AGC" occurs five times.

Individuals occasionally differ from the norm in their number of triplet copies within the short sequence — and thus the length of the sequence itself. Scientists have long linked abnormal length variations in STRs to Huntington’s disease, schizophrenia and other major diseases, but until now have never investigated repeats at the whole genome level.

In the PNAS study, which compared STRs in three well-known versions of the human genome as well as that of a chimpanzee, Molla and his co-investigators discovered a high rate of length variation in STRs that extend beyond 20 nucleotides. Their finding suggests a new set of sequences in personal DNA samples to examine for disease susceptibility.

In the process, the researchers also introduced a new, inexpensive, whole-genome method to detect abnormal repeats that could be used to screen individuals’ susceptibility to Huntington’s and other diseases.

“Our whole genome repeat study is the first of its kind,” said Molla, who specializes in computational methods for high-throughput biological data. “Our observations and proposed assay constitute a step toward understanding how these repeats work on a genome-wide scale and their implications for human health.”

A New Kind of Genetic Screening Chip
Applying computational analyses to existing sequence data, the research team compiled and assembled the first complete list of STRs in regions of human and chimp genomes where the repeated element is a triplet. For each of these regions, they compared the lengths of triplet repeats in the gene transcripts of the three human and one chimp genomes, and eventually observed a high rate of length variation in longer STRs.

The team also made a surprising discovery that could yield fresh insights about the nature of human DNA: Human genomes appear to have a strong preference for triplet repeats of length 11, 14, 17, or 20. “Dividing the lengths by three, we observed a remainder of two — one less than the length of the repeated sequence — about 100 times more than a remainder of one or zero,” noted Molla.

To find triplet STRs throughout human and chimp genomes more quickly and inexpensively in the future, Molla and his co-investigators proposed a DNA “capture array” with customized probes to adhere to all triplet repeats and their surrounding sequences in human and chimp genomes. Molla designed a new chip to perform the complex task.

Originally conceived by Kasif and Cantor, a pioneer in genomics technology, the PNAS study also includes major contributions from Kasif's first PhD student, Arthur Delcher, a senior research scientist at the Center for Bioinformatics and Computational Biology at the University of Maryland; and Shamil R. Sunyaev, Assistant Professor of Medicine and Health Sciences and Technology at Harvard Medical School and Brigham & Women’s Hospital in Boston. This study was funded by the National Human Genome Research Institute, National Science Foundation and National Institutes of Health Informatics to Bedside (I2B2) Consortium.

The BU researchers and their co-investigators next plan to analyze more genomes, refine their genome screening assay and further verify their findings.

“We are hoping to scale up the assay technology to enable us to examine STR length variations in human individuals with a particular disease, such as cancer,” said Kasif, “and to compare them to the normal population and check whether the individual has a predisposition to the disease.”

New Mentoring Program to Prep ENG Students for Post-Collegiate Life

Thu, 22 Oct 2009 00:00:00 EDT

Attention Engineering Juniors and Seniors: Ever wonder what REALLY goes on after college? Not sure how to get to where you want to be, career-wise? Do you have questions that you just don’t know who to ask?

So begins the flyer that organizers of the new Boston University College of Engineering Young Alumni Mentoring Program — Julie Young (BME’07), Stephanie Prager (MFG’08), and Annie Zavadil (BME’06,’08) — distributed on campus in September. As they get a foothold on the first rung of their own career ladders, the three recent graduates are reaching out to assist current ENG students in planning for what happens once they complete their studies.

Set to launch in early November, the Young Alumni Mentoring Program (YAMP) will pair ENG juniors and seniors with recent alumni based on career goals and interests. In a series of biweekly e-mail conversations, the mentors will advise their students on questions they may have about graduate schools and first jobs in industry. Participating students will learn about relevant classes, useful resources and instructive mentor experiences.

“BU ENG does a great job at bringing in accomplished engineers to talk to BU students,” said Young. “However, they don’t have many young alums coming back to discuss what lessons they learned during their first year out of college, what recent struggles they had to overcome and what they wished they had done while in school. The YAMP program is focused more on the next five years rather than the next 40 years.”

Participating students sign up for a minimum of six months of e-mail, phone or in-person exchanges with their mentor starting in November, but may also access other mentors via e-mail or at one or two informal networking events per semester in the Boston area. YAMP’s 23 original mentors, all friends of the program’s three organizers, represent diverse career paths and geographical locations.

Prospective junior and senior students and alumni mentors may contact the organizers at engyamp@bu.edu to find out more about the program or register. Approved mentors are required to sign up as part of the BU Career Advisory Network.

Prager and Young, both mentors of high school girls through their jobs and members of the Society of Women Engineers (SWE), conceived the program when Young appeared on a panel at an SWE event in February. After the event, a few students told Young that her advice was particularly helpful because it related directly to their career paths over the next few years, rather than 20 years out of college.

In subsequent months Prager and Young founded YAMP and invited Zavadil to join the team as a third coordinator. All three envisioned starting an e-mail exchange where young alums could share their experiences and mistakes associated with undergraduate and postgraduate life — and thus enable juniors and seniors to enter graduate school or industry with greater confidence.

In her first days on the job as a quality engineer for DePuy Spine, a Johnson & Johnson company, Prager wondered if she had sufficient knowledge of engineering and medicine to succeed.

“What I realized as I started work was that companies will always provide the necessary training for any job, and that my background from BU really did prepare me for the job,” she said. “I think that reassurance would have been great my senior year of college.”

During her senior year at BU, Young sought a non-engineering job in healthcare consulting but had a difficult time finding relevant resources. A year after she landed her first job as an analyst at Observant, LLC, a consultant advised her to always be proactive, even if that meant logging extra hours to pursue attractive projects.

“By doing so I was exposed to more aspects of the job, learned about different therapeutic areas and established myself as a hard worker who is always willing to learn,” Young said.

Assisted only in logistical matters by the ENG Alumni Relations Office and Career Development Office, YAMP has drawn an enthusiastic response from ENG Dean Kenneth Lutchen.

“As dean, one of my most gratifying roles is seeing alumni go on to have successful careers and then return to Boston University to inspire and engage the next generation of our engineering community,” Lutchen wrote in an introductory letter to prospective mentors. “The mentoring experience is one that can be incredibly valuable, and your willingness to extend a hand to current students is deeply appreciated.”