The Power of Small: Nanotechnology at Boston University's College of Engineering

The Power of Small:

Nanotechnology at Boston University’s College of Engineering

Exploiting the Power of Small At the Boston University College of Engineering, no fewer than 23 faculty members are studying the properties and behavior of nanostructures and developing new methods to fabricate and exploit them for a variety of applications. Drawing on the College’s strengths in several engineering disciplines, their research is sharpening our understanding of ultra-small phenomena and tackling some of the world’s most critical problems in health care, energy and the environment, information and communications systems, and security. Innovative undergraduate and graduate training programs are bringing that knowledge to the classroom.

Applying their expertise in the study and behavior of materials, light and biological processes at the nanometer scale, our faculty members are advancing a robust portfolio of solutions that include cheap, rapid, point-of-care diagnostics and precision-targeted anti-cancer drug treatments; better-performing solar cells and oil extraction methods; high-speed, low-power computers and optical communications systems; and ultrasensitive detectors of hazardous biological and chemical agents.

An Interdisciplinary Effort To produce such achievements, many College of Engineering faculty members collaborate with specialists in other fields. For example, biomedical engineers are teaming up with Boston University medical researchers to ensure that the nanoparticle-based medical interventions that they’re developing perform as expected in animal models.

Recognizing the value of such collaborations since its founding in 2004, the Boston University Center for Nanoscience and Nanobiotechnology (CNN) brings experts from diverse fields together in research projects, seminars, conferences, and other programs to facilitate interdisciplinary nanoscale innovation. By integrating nanoscale research at the College of Engineering and three other Boston University schools and colleges within one organization, the CNN has boosted the rate of discovery and development of powerful new technologies.

For College of Engineering nanoscience and nanotechnology researchers, “nano” may refer to the size of the particles with which they’re experimenting, the precision of motion they’re trying to achieve or the active surface on a molecule they’re investigating. They all share the conviction that the nanoscale solutions they’re advancing could lead to big changes in their fields and in the world-at-large. In the following pages, they highlight what they’re doing to make that happen.

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A new generation of technology is rising. Its high-precision tools and techniques aim to detect and fight disease with unprecedented speed and accuracy, reduce fossil fuel consumption and greenhouse gas emissions considerably, bring dramatic performance improvements and cost reductions to a vast array of electronic devices, and counter the rising threat of bioterrorism.

And that’s just the beginning.

If the technology lives up to its promise, we’ll see drugs that attack cancer cells without incurring debilitating side-effects; affordable, renewable energy devices that power entire homes; white-light LEDs that illuminate rooms and link PCs and other electronic devices to the Internet; powerful sensors that detect hazardous biological and chemical agents from trace amounts; and countless other transformative innovations.

Such technological breakthroughs may sound like the stuff of science fiction, but we are well on our way to making them real, thanks to the growing ranks of scientists and engineers who study and manipulate nanostructures—precision-fabricated entities sized between one and 100 billionths of a meter. Leveraging the unique mechanical, chemical, electrical and optical properties of these atomic-scale materials as well as their ability to penetrate biological systems at the sub-cellular level, nanoscale researchers are making great strides in addressing big challenges that range from infectious disease pandemics to global climate change.

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Advancing Nanoscale Solutions to Critical World Problems

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Research At-a-Glance

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High-performance biosensors and LEDs Assistant Professor Hatice Altug

Tracking single biomolecules Assistant Professor Sean Andersson

Deformable mirrors for optical devices Professor Thomas G. Bifano

Optoelectronic chips and biosensors Assistant Professor Luca Dal Negro

Pathogen detection Associate Professor Kamil Ekinci

Novel materials and disease biomarker discovery Professor Bennett Goldberg

Site-specific drug delivery to lung cancer tumors Professor Mark Grinstaff

Transdermal, needle-free inoculation Professor Mark Horenstein

Carbon nanotube assembly Assistant Professor Ramesh Jasti

Robust coding for secure and reliable nanosystems Assistant Professor Ajay Joshi

Point-of-care molecular diagnostics Assistant Professor Catherine Klapperich

Associate Professor Amit Meller

High-powered optical fiber lasers Professor Theodore Morse

Quantum dot-enhanced LEDs and solar cells

Computer-aided design of nanodevices Assistant Professor Harold Park

Ultrasound-based cancer treatment Assistant Professor Tyrone Porter

Nanoparticle-enhanced imaging and therapy Professor Ronald Roy

Drug screening on a sound-driven biochip

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Professor Theodore Moustakas

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Fast DNA sequencing and disease diagnosis

Assistant Professor Matthias Schneider 3

Probing the impact of forces on critcal cell proteins Assistant Professor Michael Smith

Optimizing carbon nanotubes for optics applications Associate Professor Anna Swan

Detecting semiconductor circuit defects and biomolecular interactions Professor Selim ĂœnlĂź

Nanoparticles for heart disease detection and oil exploration Associate Professor Joyce Wong

Detection and imaging of complex biological processes Associate Professor Xin Zhang

Light Sensitivity

We’re developing a label-free, realtime, multiplexed detection system with unprecedented sensing capabilities. This lab-on-a-chip platform could be used in highperformance biosensing and drug discovery applications.

Assistant Professor 4

Hatice Altug (ECE)

Enhancing Detection Capability With operational wavelengths covering the visible to infrared range of the electromagnetic spectrum, the optical biosensors we’re developing can detect biomolecules at the nanoscale and could be extended for chemical detection as well. We use vibration spectroscopy and other optical resonance-based detection techniques, and employ nanostructures to significantly enhance biosensor sensitivity.

The nanostructures we’re fabricating include photonic crystals (dielectric nanostructures) and plasmonics (tiny metallic nanostructures), and a combination thereof. These structures enable us to manipulate light on a chip efficiently by localizing light and enhancing electromagnetic field intensities to an unprecedented level. As a result, we can enhance our capability for detecting proteins, viruses or other biomolecules.

We’re also integrating nanobiosensors and nanofluidic channels as a single entity to manipulate light and transport liquids on the same platform. This new system is enabling us to actively deliver biomolecules to the nanosensor surface.

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With their unprecedented sensing capability, our on-chip platforms could be used to detect, for instance, a single virus or protein molecule. Because they are designed to screen several proteins or viruses simultaneously in real-time, they could also be used to investigate drug-binding site interactions critical to drug applications and point-of-care virus screening. Scientists could also work with the platform to study how proteins interact.

In the next five years, our main goal is to use these platforms to promote a better understanding of proteins and their interactions, so we gain insight into the mechanics of how cells work and shift from healthy to diseased states, and can develop drugs accordingly. We’ll eventually focus on developing a chip to screen multiple viruses and other pathogens in real-time.

We’re also using the photonic and plasmonic nanostructures to develop novel LEDs at the NSF Smart Lighting Center at Boston University, particularly for biosensing applications.

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From Drug Discovery to Smarter Lighting

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Vibrational signatures of protein molecules can be dramatically enhanced by strategically arranged arrays of rod-shaped nanoantennas.

Tracking Biomolecules

Our research centers on developing and applying new instrumentation for studying dynamics in systems with nanoscale features, especially proteins and other biomolecules.

These tools could help improve our understanding of biological processes and lead to new medical advances.

Assistant Professor 6

Sean Andersson (ME) From Static to Dynamic Imaging Two well-known biological imaging techniques—atomic force microscopy (AFM) and confocal fluorescence microscopy (CFM)—perform well in capturing static phenomena, but are far too slow to image dynamic biological processes. We’re reconfiguring AFM and CFM with new software algorithms to perform high-speed, high-resolution dynamic imaging so we can track the behavior of single molecules in solution, and, eventually, in living cells.

Both techniques use a point-like sensor which moves back and forth in a raster scan, sampling point-by-point to build an image, pixel-by-pixel. AFM uses a sharp, 10-nanometer-radius tip to interact with a biological sample; CFM uses a detection volume that’s also small relative to the sample size.

To track a dynamic process such as a protein’s action within a cell, we don’t necessarily need to build image by image and track changes from one image to another, because we’re Simulation results of high-speed AFM interested in a single protein or nanoscale process that occupies imaging. Image shows the trajectory of only a small part of the image. So what if we could take a single the AFM tip produced by Andersson’s non-raster scanning algorithm (black) sensor and, rather than raster it to build a complete image, use superimposed upon a standard rasterscan image of DNA (in false color). it to follow a dynamic process as it occurs?

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To develop high-speed AFM, we’re currently focusing on dynamic processes that occur along string-like biopolymers. Based on measurements of biomolecules that we obtain from the AFM tip, we adjust where we want to go so that we stay near that string at all times. As a result, we end up with a fraction of the data that a conventional AFM raster scan would generate, substantially reducing the time it takes to build a complete image. We’re now developing collaborations with the Boston University School of Medicine (BUSM) to use our AFM method to study the role of a protein on actin that enables muscular motion.

To accelerate CFM and effectively obtain a wide field of view of a dynamic process, we move the instrument’s detection volume through a feedback process. Based on the measurements we get from the fluorescence of what’s moving, we move the detection volume to follow the action. We’re currently applying the method to freely diffusing quantum dots and moving toward tracking labeled molecules inside living cells.

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High-Speed Tracking

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Magical Mirrors I make electrically actuated mirrors with hundreds to thousands of optical surfaces controlled to nanoscale precision. Used in optical devices ranging from microscopes to telescopes, these “deformable” mirrors can improve the resolution of an image when there’s an aberration source.

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Director of the Boston University Photonics Center Professor

Thomas G. Bifano (ME)

The slight index of refraction caused by the Earth’s atmosphere not only makes the stars twinkle, but blurs any image of them taken by a ground-based telescope. I make mirrors with adaptive optics that can counteract that effect, effectively “untwinkling” the stars.

Similarly, an ophthalmologist seeking to examine your retina through the misshapen lens and cornea can use my deformable mirrors to pre-compensate a microscope before it looks into your eye. With this technology we can now see cellular-level structures in the eye.

Deformable Mirrors for Everyone In the past 12 years, we’ve significantly increased the capability of deformable mirrors—from nine-actuator arrays operating at one Hz speed to 4,000-acuator arrays at 30 kHz. We’ve also reduced their cost from $1,500 per actuator to $150. A 30-meter telescope needs up to 10,000 actuators, so our actuators could lower the cost of each mirror from $15 million to $1.5 million.

To advance this technology, we have partnered with Thorlabs, the world’s leading optical components company. In this year’s catalogue, they sell an Adaptive Optics Kit with the Boston University-developed deformable mirror. That puts this capability in the hands of a million creative individuals rather than just two or three professors.

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Today we’re evolving these mirrors to meet the increasingly exacting needs of optical instrument designers, from biomedical scientists and clinicians who require compact, high-resolution, adaptive optics to conduct molecular-level or endoscopic investigations, to astronomers who seek high-contrast mirrors to block starlight so they can detect exoplanets.

For example, Jet Propulsion Laboratory scientists recently sought high-contrast mirrors to block starlight and enable the detection of exoplanets. They needed one billion times less light from a given star to reach the telescope. That translates to 300 segments of the mirror which could tip and tilt and piston at nanoscale precision, with each segment about 400 microns wide. We came up with an electromechanical design that achieves nanometer tolerance, assembled and tested the mirror in collaboration with a MEMS foundry and Boston Micromachines (a company I helped found that’s currently the leading deformable mirror producer in the U.S.), and delivered it in 2009.

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Bringing Objects Near and Far into Focus

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Close-up measurement of interferometric microscope image of a portion of a large, 1020-segment deformable mirror, showing surface roughness of about three nanometers on the flattened segment. Mirror was designed for a defense telescope used to track satellites

Hybrid Chips We focus on the nanofabrication, optical characterization and electromagnetic design of metal-dielectric nanomaterials and nanostructures for on-chip nanophotonics applications. In particular, we develop efficient nanoscale light sources, optical sensors and laser structures based on the unique behavior of optical fields confined in nanoscale complex media.

Assistant Professor 10

Luca Dal Negro (ECE) Light-Emitting Silicon Nanostructures Today’s photonics devices rely on expensive semiconductor materials that emit light efficiently but cannot be integrated in silicon-based microelectronics. Our challenge is to take siliconcompatible materials and engineer their optoelectronic properties to demonstrate efficient light emitters on the nanoscale. We envision optics and electronics components within the same silicon chip on a high-density platform, one that could lead to inexpensive, highperforming, mass-producible, electrical and optical devices.

This vision can enable an inexpensive, integrated silicon chip with thousands of waveguides, modulators, detectors and other optical Images represents light scattering components controlled by standard microelectronics circuitry. from nanoscale aperiodic surfaces Our ultimate goal is to design and engineer optical sensors and fabricated in Dal Negro’s group. light sources for optical communication and optical chip-to-chip communication inside a computer. Conventional PCs are limited by interconnects that heat up at high current and degrade their performance. The use of optics to strongly reduce heat dissipation and communicate at the speed of light could boost processing speed 1000-fold over what’s possible with integrated electronics. Nanostructured silicon can enable all of this within an inexpensive approach with large scalability and manufacturability.

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The physics of light diffusion through a complex medium opens up the possibility for creating strongly localized optical waves that slow down light to enhance light-matter interaction on the nanoscale. By engineering the shape and size and arrangement of nanoparticles to scatter light on twodimensional surfaces in a strategic manner, we can boost the performance of current optical biosensors, photo-detectors and other active photonic devices.

We’ve demonstrated the ability to design and engineer complex arrangements of nanoparticles which support strongly localized electromagnetic fields. Using enhanced light-matter interaction effects on the nanoscale, we can efficiently detect a wide range of biochemical analytes within a robust and reproducible approach that leverages on the control of multiple light-scattering and localization phenomena in engineered optical chips.

Potential applications include biosensors capable of detecting harmful bacteria, viruses and food and water contaminants with greater reliability and lower error rates than current technology. We are also investigating this technology to realize energy concentrators and solar cells to enhance solar energy capture over broad energy spectra.

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A New Platform for Nanoscale Optical Sensing

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Diving for Pathogens

We are designing diving-board-like cantilevers to detect trace amounts of pathogens in a fluid. The textured surfaces of these special cantilevers mitigate the inherent stickiness of water and other fluids, thus optimizing signals received from any pathogens onboard.

Associate Professor 12

Kamil Ekinci (ME)

Cantilever Detectors If a pathogen attaches to one of our vibrating, nanoscale diving boards, the board will become heavier and its resonant frequency will decrease. By bouncing light or radio waves off these boards, we can detect this reduced frequency and thus detect the pathogen. The advantage of creating these tiny structures at the nanoscale is that you can even detect biochemical targets sized on the order of a molecule.

We’ve gotten these boards to work in vacuum and in air, but in many cases you want to detect a biomolecule in a fluid, such as a blood sample. If you put a diving board in a biochemical fluid, however, the fluid sticks to it and dampens its vibrational motion. The same effect could be observed by hitting a tuning fork in water: its vibrations die down much faster than in air. To make an Ekinci’s lab is developing diving-board-like effective biochemical sensor, we need to mitigate this cantilevers to detect trace amounts of pathogens in water. The textured surfaces are designed to damping and optimize the small signal coming from overcome water’s inherent stickiness, which the presence of a pathogen molecule. inhibits the devices’ sensitivity.

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Pinpointing Pathogens Our ultimate goal is to make a diving board with functional units on it that will catch pathogens in a water solution and signal their presence. The device and the signal it produces are quite small, so we need a way to amplify the signal, but the signal we’re looking for becomes quite suppressed in fluid.

So we designed super-hydrophobic structures that minimize interaction with the water. We have engineered the cantilever so that when we submerge it in water, air is trapped on it; for the most part, it moves as if in air. As a result, the damping effect is minimized and the source becomes easier to detect. These cantilevers are very sensitive and could be used to detect proteins, viruses, bacteria, DNA and other biomolecules, including potential bioterror agents.

We now have our first proof-of-concept that we can actually enable the cantilever to move in water as if it’s moving in air, but we haven’t actually detected biomolecules yet. In the next three years we plan to put functional units on the diving boards to enable them to detect traces of specific biomolecules.

Probing Hidden Worlds

My primary areas of focus are the nanoscale physics of materials that exhibit novel properties because of their very small scale, and protein microarrays for disease diagnosis and monitoring and biomarker discovery.

Director of the Center for Nanoscience and Nanobiotechnology 14

Professor

Bennett Goldberg (ECE)

Nanotechnology Research BU College of Engineering

First discovered in 2004, graphene is composed of a single atomic layer of graphite.

One of the strongest known materials—rivaling the diamond—it can stretch 20 percent of its length before breaking. It also exhibits high electrical and thermal conductivity, and could be used in applications from pressure sensors to flexible electronic displays to transparent electrical coatings for solar cells and windows.

[Professor] Anna Swan (ECE) and I are studying graphene’s structure. Using tools we’ve developed such as high-resolution Raman scattering spectroscopy, we’re examining how its atoms vibrate and carry energy, and how it conducts electricity.

Based on our findings, we’re developing a graphene-based membrane for a pressure sensor that might work in harsh environments, such as down bore holes in oil, gas, aquifer and other deep-underground settings. In the next two years, we hope to have demonstrated a graphene pressure sensor that could be adapted for industrial use.

Experimental tools we’ve developed are critical to novel measurements that provide new insights about the structure of graphene and other nanomaterials. These include a tip-enhanced near-field microscope, which uses a very sharp nanoscale metal tip scanning over a surface to measure the local optical response, and a nanoscale spectroscopy technique that can measure properties of materials such as graphene and carbon nanotubes.

Multi-layer graphene.

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Understanding and Exploiting Graphene

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Finding Disease Biomarkers Protein microarrays are currently used for diagnosis and detection, but they could one day be used to probe cells and discover new biomarkers for specific diseases.

By combining a label-free protein microarray with a mass spectrometer, [Professor] Selim Ünlü (ECE) and I are working to determine exactly what the molecular species the various probes on the microarray surface find in cells and serum— information that could lead us to identify new disease biomarkers.

In a parallel effort, we also envision the use of our protein microarrays for inexpensive and robust point-of-care disease diagnosis and monitoring in resourcelimited settings. We’re developing customized “biomarker” arrays to detect disease-specific anomalies in protein regulation at the cellular level.

Targeting Tumors

We’re exploring the use of nanoparticles in the delivery of anticancer agents for the treatment of various cancers.

The idea is to take advantage of unique nanoscale properties to increase the efficiency of drug delivery.

Professor 16

Mark Grinstaff (BME)

The leading cause of cancer mortality in the U.S., lung cancer accounts for about 160,000 deaths— 28 percent of the nation’s total cancer deaths—each year. One of the problems in lung cancer is recurrence. The standard of care is to remove the cancer surgically, but the recurrence rate is 10 to 20 percent, with a five-year survival rate after a successful resection on the order of 50 percent.

Our idea is to resect the tumor and apply the nanoparticles during the surgical procedure, so we can deliver a high, local concentration of the chemotherapeutic drug at the diseased tissue site.

Polymer film on surgical collagen scaffold. Upper panel shows a dry film; lower panel shows flexibility of a wet film.

Scale bar: 5 mm. (Source: Annals of Surgical Oncology)

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We’ve created a polymeric nanoparticle that’s approximately 100 nanometers in diameter that can be loaded with an anticancer drug such as paclitaxel (Taxol). When it enters a cell, this nanoparticle undergoes a conformational change and can expand from 100 to 1000 nanometers in size. When it swells to 1000 nanometers, it releases the drug within the cell.

In mouse models, we make an incision, inject about 750,000 tumor cells and follow with treatment. We have found that when we use our nanoparticles loaded with paclitaxel, we don’t get tumors, but when we use the drug by itself, we do get tumors. It doesn’t work as well without the nanoparticles because the drug does not stay at the cancerous site and gets dispersed readily.

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Nano-Precision Drug Delivery

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Toward Clinical Trials Initially funded by the Center for Integration of Medicine and Innovative Technology in 2007 as a research collaboration between my lab and that of Dr. Yolanda Colson, a thoracic surgeon at Brigham and Women’s Hospital, this is the first example of the use of nanoparticles with expansile capability.

Our goal is to take these materials into a larger animal model and see how they function, and consider a potential clinical trial after safety studies are completed. We estimate it will take about five years to get this into the clinic. Our hope is that any time cancer is resected from lung tissue, this procedure would be used as a way to lower the rate of recurrence.

Rapid-Fire Inoculation

We are developing a method for transdermal, needle-free drug delivery in which drug-laden nanoparticles are forced into the skin using an electrostatic pulse. If successful, the technique could be used for the rapid inoculation of mass populations, or as a preferable alternative to ordinary drug delivery.

Professor 18

Mark Horenstein (ECE)

Lots of people have worked on transdermal drug delivery using a variety of methods, but all methods either require using micro-needles or dose very slowly. Our approach avoids these drawbacks and may ultimately permit the rapid inoculation of large populations.

For our method to be successful, however, it must surmount three challenges: (1) Can we encapsulate drugs into nanoparticles? (2) If we get these drugs and proteins into the skin layer, will the immune system cells ingest them? (3) Can we drive these nanoparticles into the skin using electrostatic forces?

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To inoculate someone rapidly, one must direct a vaccine into the stratum corteum, the system of cells lying just under the outer skin layer that has a direct pipeline to the immune system. We charge drug-encapsulated nanoparticles and apply an electric field pulse to drive them about 10 microns below the outer layer of the skin, where the stratum corneum resides. We’re trying to create a strong enough field to porate the skin, thereby allowing the nanoparticles to penetrate the skin cells and reach the appropriate layer.

Once the particles are inside the skin, my collaborator David Sherr [professor of public health at Boston University] tracks their pathway to the immune system in laboratory mice. In this phase of the work, we’re trying to show that the dendritic cells in the stratum corteum ingest the nanoparticles and transfer them to the immune system.

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Getting Nanoparticles Under the Skin

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Fluorescent dye helps track the movement of nanoparticles through the body.

Engineering a Portable Field Instrument One long term goal is the development of a portable field instrument that can be used in a doctor’s office or by an emergency medical technician for the painless and rapid inoculation of large populations in the event of a bioterror attack.

If we can demonstrate the basic biology and physics of our approach, the next step would be to engineer a viable product.

We’ve learned that the piece of the puzzle we have not yet solved—driving nanoparticles into the skin with electrostatic force—is more complex than we originally envisioned, and we are now focusing on that aspect of the problem.

Bond by Bond

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Depending on the arrangement of carbon atoms, or chirality, carbon nanotubes exhibit unique properties that make these singlemolecule structures attractive for engineers seeking to design faster computers, higher-resolution sensors and other highperformance technologies. We Assistant Professor ultimately want to Ramesh Jasti (MSE) make large numbers of distinct types of carbon nanotubes on demand, just as pharmaceutical companies assemble drug molecules—by constructing them bond by bond.

Hollow carbon wires sized about 50,000 times narrower than a human hair, carbon nanotubes are hard to make in large quantities with desired electronic, optical and other properties. To configure carbon nanotubes to make faster electronics and other higher-performing technologies for the commercial marketplace, you will need to make them with the same precision as silicon wafers and be able to mass-produce them easily. Today they’re made in batches at very high temperatures, with only a small fraction exhibiting the desired properties.

Nanotube Assembly, Two Carbon Atoms at a Time

Nanotechnology Research BU College of Engineering

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When I was a post-doc at the University of California, Berkeley, we made the first small segment of a carbon nanotube, a hoop-shaped chain of benzene molecules which could potentially serve as a template, or base structure, for growing a full-length carbon nanotube with a predefined diameter and chirality.

Our challenge today is to extend these segments into long cylinders while maintaining atomic-level structural control to achieve specific properties.

To get there, we have to invent reactions to make micrometer-scale structures. Our lab has just begun to make different types of carbon nanotube templates. The segment we made at Berkeley would lead to a metallic nanotube; we’re now making segments that could form the basis of a semiconducting nanotube. In all cases we’re looking at reactions between two carbon atoms at a time to build upwards to a single carbon nanotube molecule.

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The Jasti Group uses standard solution phase organic chemistry techniques to prepare carbon nanotubes.

Carbon Nanotubes on Demand Conceptual demonstrations indicate that carbon nanotubes could be used in fasterperforming electronics devices; more powerful sensors for biohazards and explosives; water desalination; a more efficient electric power grid; and enhanced solar energy applications.

Based on our approach to high-precision, organic synthesis of carbon nanotubes, I envision that I and three or four other major players in this area will eventually solve this problem. In the next 10 to 15 years, I expect you will be able to buy any kind of carbon nanotube you want, and a variety of carbon nanotube-based devices will come on the market.

Robust Nanosystems

We are exploring the use of carbon nanotubes for on-chip computation. Our goal is to develop an integrated circuit– system solution that combines nonlinear coding and physical design to improve the reliability and security of nanoscale systems.

Assistant Professor 22

Ajay Joshi (ECE)

From Circuit to Systems Design With complementary metal–oxide–semiconductor (CMOS) technology expected to reach miniaturization limits in the next five to ten years, it has become extremely important to identify a promising replacement. Various new nanotechnologies such as carbon nanotubes (CNT), graphene nanoribbons, spintronics and nanophotonics have been proposed.

Though research has shown the advantages of these nanotechnologies over CMOS, current nanomanufacturing techniques result in highly unreliable and unsecure large-scale systems. We propose an integrated circuit–system solution in which we use nonlinear coding along with physical design to improve the reliability and security of nanoscale systems.

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CNTs exhibit semiconducting or metallic behavior, and hence can be used as transistors or wires, respectively. However, as it is difficult to grow metallic and semiconducting tubes in a deterministic fashion, we get unreliable devices. For example, a memory cell built using CNTs can have permanent and/or transient faults due to the presence of metallic CNTs. The metallic CNTs could potentially be removed, but if the removal process is not controlled, the semiconducting CNTs could also get removed, resulting in open circuits. The resulting transient and permanent errors produce nanosystems that are unreliable and thus less secure.

While engineers have long used linear coding and replication techniques to detect and correct hardware errors, these techniques focus on the most probable errors, and cannot guarantee protection against other classes of errors.

These techniques are therefore inefficient or even unsuitable in situations that range from repeating errors to unpredictable error rates.

We are investigating the use of nonlinear coding techniques for designing reliable and secure nanosystems for two reasons. First, nonlinear codes provide uniform coverage across all errors using the same number of redundant bits as linear codes. Second, their data-dependent error detection properties provide an opportunity to improve error detection probability for errors that repeat over consecutive cycles through the use of novel physical design techniques.

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Robust Design for CNT-Based Systems

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Diagnostics-on-a-Chip

We’re developing a robust, inexpensive, handheld plastic chip that extracts DNA using nanoparticles and could enable rapid, point-of-care diagnostics for infectious diseases without the need for electricity or refrigeration.

The chip could be a major step forward in facilitating molecular diagnostics in developing countries.

Assistant Professor 24

Catherine Klapperich (ME, BME)

Rapid Sampling and Analysis For some molecular diagnostics, only a small amount of sample from the patient is needed. Our goal is to shrink assays down to the microliter, or hundreds-of-nanoliter level.

We’re working to develop a robust, inexpensive, easy-to-manufacture microfluidic chip that integrates sample preparation, amplification and detection. The chip uses a micron-sized, “micro solid phase extraction column” to grab and concentrate nucleic acids from a few hundred microliters of blood or other bodily fluid.

Embedded in the column are particles sized a few hundred nanometers in diameter—and we’re continuing to drive the particle size down to increase surface area-to-volume ratios. Because these nucleic acid binding or grabbing events occur at the surface of the nanoparticles, the more surface area you have, the more DNA or RNA you can extract— which may lead to smaller sample sizes needed to detect disease.

Prototype for powerless, portable extraction and storage of nucleic acids from blood includes a straw containing a matrix for isolation and storage of HIV RNA, a routing block for collecting a pinprick of blood and introducing solutions, and a bicycle pump for driving liquid through the device. The project is a collaboration between Drs. Klapperich, Andre Sharon (ME/Fraunhofer USA Center for Manufacturing Innovation (FHCMI)), and Alexis SauerBudge (BME/FHCMI).

(Source: FHCMI)

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The column could ultimately be used for the collection and storage of samples potentially infected with bacteria and other infectious particles in small samples of blood, urine and other body fluids. It’s especially well-suited for use in poorer, rural communities because the extracted genetic material does not require expensive refrigeration or electricity, and the device is portable and easy to use.

With NIH funding, we’re now studying influenza A, which includes potentially pandemic strains such as the novel H1N1, and influenza B, a seasonal flu variant. Our goal is to design a chip to detect and differentiate between the different types of flu. NIH has also funded a project to study infectious diarrhea, the world’s number one killer of children. Because it can spread easily and rapidly, it’s important for clinicians to diagnose it quickly, but current tests take at least two days.

Our chip may eventually reduce that time to one hour.

We’re also developing a version of the chip to enable physicians to immediately extract viral RNA from blood infected with HIV. This customized chip would perform viral load measurements to help physicians assess the status of the disease in the patient.

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Point-of-Care Applications

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Faster Genome Sequencing

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Routinely used to produce enough copies to enable the detection and sequencing of DNA molecules, molecular amplification methods such as PCR (polymerase chain reaction) are expensive, time-consuming and error-prone. Using our nanopores—two-nanometer-wide, nearly cylindrical, silicon nitride sensors that electronically probe DNA molecules as they pass Associate Professor Amit Meller (BME) through the pore—we’re developing fast, accurate, inexpensive, methods for amplification-free detection and sequencing of individual DNA molecules. This research could have farreaching implications ranging from basic biological science to disease diagnosis.

The longer the DNA strand, the faster the end finds its way to the nanopore.

Point-of-Care Virus Detection We’re also combining our nanopores with synthetic DNA probes known to invade DNA molecules in a specific manner as a means of virus detection. Threading DNA molecules inside the pore, we can see distinct marks to indicate we’ve invaded a viral rather than a standard human genome. We predict that within seconds of running a minute DNA sample through the pore, a physician could detect a virus’s genome in a blood sample.

Finally, we’re using our nanopore devices to address fundamental questions in genetics and biophysics. We’re trying to map the positions of transcription factors— proteins used to regulate the transcription of certain genes—along genomic DNA. By pinpointing where transcription factors are bound on a long piece of DNA, we can determine the sites where specific genes are activated. We can design the pore so that if we thread the genomic DNA through it, we can look at the ion current signature as the DNA moves through the pore and map where the transcription factors are bound.

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We’re developing an electrically-based nanopore sensor that utilizes the fact that most biological molecules are strongly charged. Based on our understanding of the electric field distribution near the pore and our ability to manipulate this field to increase the DNA capture rate, this method allows us to enhance DNA molecule detection sensitivity by orders of magnitude. As a result, we can reduce the typical DNA sample size from about one billion molecules down to 100,000.

There’s no reason why we couldn’t probe DNA molecules with thousands of pores, a development that could enable us to sequence the human genome in a matter of a few hours. Such fast, cheap genome sequencing will not only bring personalized medicine into reality but also significantly enhance our ability to probe how cells behave and accelerate drug discovery.

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Fast. Cheap, Single-Molecule Sequencing

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Industrial-Strength Lasers I’m interested in sintering nanoparticles into Higher-Order Mode (HOM) fibers, which are capable of stable propagation of light for use in high-powered optical fiber lasers for materials processing, military objectives and other applications. My research may lead to a multi-kilowatt laser that operates at significantly higher power levels than what conventional single fundamental mode fibers can accommodate.

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Professor

Theodore Morse (ECE) It is a high military priority to produce weapons-grade optical fibers that can withstand the levels of energy density delivered by high-powered fiber lasers. Such fibers would have to sustain a much greater power output per unit area than what their lower order mode counterpart, the single fundamental mode LP01 fiber, can sustain.

HOM fibers that have larger core area, and thereby receive less Aerosol combustion synthesis. The nanoscale particles collect on the energy density per deposition rod forming a rigid soot body unit area, offer an (tube) that is removed from the rod before processing. attractive solution.

Turning Up the Power This research could result in a multi-kilowatt laser that emits orders of magnitude greater power than lasers that use LP01 fibers.

Such a laser could be used for not only for military purposes, but also in materials processing, welding and other industrial applications. While some problems with Outside Vapor Deposition (OVD) remain to be worked out, we envision a fiber laser that will produce five to 10 kilowatts in the next three to five years.

This research is funded by the Department of Defense’s High Energy Laser Joint Technology Office and the Office of Naval Research, and conducted in collaboration with Lucent Technologies and Optical Fiber Solutions.

Nanotechnology Research BU College of Engineering

The use of HOM propagation enables the development of an erbium–doped fiber, which provides high efficiency, small quantum defects leading to high pump utilization efficiency, and no photo-darkening, which keeps light losses low. We fabricate fibers with very large core areas—6,000 square microns, as compared to under 100 square microns for LP01 fibers—of highly pure, doped silica. Erbium can be pumped, or energized, with multi-mode diodes that provide more power than single-mode diodes.

Rather than producing each fiber with conventional fiber fabrication methods, in which the doped core layers are formed on the inside of a substrate tube, we use a much simpler, outside aerosol deposition (OAD) technique.

OAD sends aerosol droplets into a flame, producing solid elements (the nanoparticles), water and carbon dioxide. The nanoparticles permit the sintering into a hightransparency, pore-free glass.

bu.edu/eng

A Wide Area Solution

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Quantum Leaps

Sized on the order of 10 nanometers across, semiconductor particles known as quantum dots exhibit unique properties that we’re exploiting to make green LEDs and to develop highly efficient solar cells. Our research could lead to significant improvements in white light LEDs and solar-electric conversion efficiency.

Professor 30

Theodore Moustakas (ECE)

Improved White Light LEDs Green LEDs are the weak link to developing LED-based white light for general lighting applications. To produce this white light, blue, green and red LEDs must be combined, but making green LEDs is currently a very inefficient process.

We have preliminary results that support the idea that quantum dots are the route to resolving this “green gap.” One of my graduate students, Tao Xu (ECE’07), described the science behind this in her PhD thesis and made prototype green LEDs. To resolve the green gap and develop other applications such as more efficient solar cells, we want the composition of the quantum dots we’re using to be in the form of indium gallium nitride, where indium Green LEDs based on indium gallium nitride accounts for about half of the material. quantum dots.

Nanotechnology Research BU College of Engineering

First-generation solar cells are made with a silicon “PN” junction, a material with two layers—P-type on top, and N-type on the bottom. The problem with commercially available solar cells is that they cannot absorb a significant part of the solar spectrum. Their maximum efficiency—how much absorbed light gets converted to electricity—is about 24 percent in the lab, but in practice it’s much less. Part of this is because silicon rejects the infrared end of the light spectrum, which ranges from ultraviolet to infrared.

Second-generation solar cells are called “tandem” solar cells, and consist of multiple cells stacked on top of each other. They absorb more light and thus produce more electrical energy.

Generally produced from gallium arsenide, these cells have demonstrated an efficiency of up to 39 percent in the lab, and have been utilized in very expensive applications such as power generators for satellites.

At our lab and elsewhere, engineers are trying to develop thirdgeneration solar cells aimed at producing at least 50 to 60 percent efficiency at low cost. Our approach is to use indium gallium nitride quantum dots between the P and N layers of a single P-N junction. The quantum dots will be of different sizes and thus absorb the plurality of the solar spectrum, and are expected to yield 63 percent efficiency under concentrated light.

bu.edu/eng

More Efficient Solar Cells

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Nano-CAD

If successful, my research will enable scientists and engineers to study and design nanomachines, nanodevices and nanostructures computationally, similar to how design engineers routinely use computer-aided design tools to design bridges, buildings, airplanes and submarines.

Assistant Professor 32

Harold Park (ME)

Military engineers routinely test missiles on a computer rather than on the launch pad, because they understand the properties of the materials and building blocks they’re using. For materials designed at the nanoscale, we don’t necessarily understand their properties as they get smaller. And without that knowledge, we can’t necessarily make anything useful out of them.

For example, to make a smaller computer chip, you have to use smaller copper wires. But as you scale the wires down in size, will they be better or worse at conducting heat? Will a wire break because it’s so small? You can’t predict the wires’ performance in an application without first generating knowledge about how the material behaves.

failures, such as the propagation of cracks, in new materials.

Predicting Material Behavior from the Nanoscale On Up If all goes well, my research could allow engineers to, for example, design an airplane but control the properties of its materials from the scale of atoms to doors and wings.

They would know how the plane would behave at a smaller and smaller scale, and how that would impact it at the larger scale. By using multi-scale modeling to gain more knowledge of and control over a material’s properties at all sizes, designers would be able to predict more easily how it would behave and when it would fail.

Our goal is to enable engineers to run simulations on the desktop within minutes, rather than using a supercomputer over days or weeks. In pursuit of that goal, we’re now trying to understand better how different properties couple at the nanoscale.

Nanotechnology Research BU College of Engineering

Using computational methods, we can model nanomaterials to improve our understanding of their properties, determine how strong they are and how well they conduct heat, and then start building things with them. Rather than investing a lot of time and money in several iterations of actual building and testing, engineers could work with these models to obtain better performing, more reliable technology at much lower cost.

Such models must take into account the large surfacearea-to-volume ratio that nanomaterials exhibit. As you make materials smaller and smaller, there are fewer atoms in the middle of the material and more atoms on its surface, resulting in different properties.

Multi-scale modeling can reveal potential

bu.edu/eng

Accelerating the Pace of Design

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Sounding Out Cancer

My group is combining nanotechnology and biomedical ultrasound to treat solid tumors in a site-specific manner, through novel drug delivery and thermal ablation techniques.

Assistant Professor 34

Tyrone Porter (BME, ME)

Treatment options for solid tumors include surgery, which is invasive and often requires a lengthy recovery, and chemotherapy, which is damaging to healthy tissue and can compromise the immune system. Our Medical Acoustics Laboratory is developing techniques that combine nanotechnology and focused ultrasound to kill localized malignancies rapidly with surgical precision or deliver chemotherapy in a targeted manner.

Nanotechnology Research BU College of Engineering

The first technique involves encapsulating chemotherapeutic drugs in polymer-modified, temperature-sensitive liposomes, and triggering drug release with ultrasound-mediated hyperthermia. The temperature-sensitive liposomes are designed to accumulate within solid tumors after being injected into the bloodstream.

The drugs are delivered by spherical carriers with an average diameter of 100 to 300 nanometers, which is an ideal size for extravasating through leaky tumor vasculature and accumulating at the tumor site. The idea is to sequester, package and localize the drug so that it’s not exposed to healthy cells and tissues, and use polymers to reduce the threshold temperature needed to release the drugs.

By using ultrasound to elevate the temperature locally within the tumor, the liposome shell will be disrupted and the drug will be released only in the tumor.

Using this approach, we can increase the concentration of chemotherapy delivered to tumors without increasing the systemic toxicities.

bu.edu/eng

Ultrasound-Heated Drug Release

35 Polymers reduce the threshold temperature required by temperature-sensitive liposomes to release chemotherapeutic drugs.

Nanodroplet-Enhanced Tumor Ablation Additionally, we are producing liquid perfluorocarbon nanodroplets designed to accumulate within solid tumors after being injected into the bloodstream. Once localized at the tumor site, the nanodroplets can be vaporized noninvasively with high-intensity focused ultrasound pulses. The resultant vapor bubbles are used to increase the absorption of focused ultrasound at the tumor site.

As a result, the amount of acoustic power and exposure time required for destroying the tumor via thermal damage is significantly reduced.

Vaporization of the nanodroplets and the activity of the resultant bubbles can be monitored with diagnostic ultrasound, which presents the possibility for image-guided ultrasound therapy of solid tumors.

Image and Treat We use nanoparticles in conjunction with laser light and focused ultrasound to image tissue structures and/or thermally lesion tumors and other diseased tissue more precisely and reliably.

Professor

Ronald Roy (ME) More Precise Therapy 36

High-intensity focused ultrasound (HIFU) can project acoustical energy into tissue and generate localized heating at depth—literally “cooking� the region of exposed tissue. A key challenge in HIFU therapy is to heat targeted tissue volume accurately with minimal damage to surrounding tissue.

One approach is to induce small amounts of cavitation, forming microscopic bubbles that help convert acoustical energy into heat. Laser-irradiated nanoparticles promote cavitation by providing nucleation sites: a single flash of laser light heats the particles, forming nano-scale vapor cavities that evolve into a cavitation bubble field when exposed to HIFU. The heated nanoparticles enable controlled cavitation production more precisely and with less ultrasonic energy. And because their surface properties can be modified so they adhere to specific tissue types, they also provide a supplemental means for targeting; you get an effect only where light, sound and nanoparticles co-exist.

An Integrated Clinical Tool We envision a single apparatus that switches from imaging mode (short acoustic pulses) to therapy mode (long pulses) with the turn of a dial. This work draws on a collaboration with current and former Mechanical Engineering professors Glynn Holt and Todd Murray, focused on the physics governing the use of nanoparticles to enhance photoacoustic imaging and HIFU therapy ex vivo. Our next step is to demonstrate the effectiveness of this technique in vivo.

Nanotechnology Research BU College of Engineering

In photoacoustic imaging, you expose tissue to a short flash of laser light that is preferentially absorbed by specific tissue types, most notably blood vessels.

These tissues heat and expand, launching acoustic waves. By monitoring the production of these tissue-specific acoustic waves, you can pinpoint where the heating occurs.

Unfortunately, light that enters tissue is scattered and absorbed, rapidly diminishing in intensity—compromising the ability to obtain a photoacoustic response at greater depths, where tumors often reside. A nanoparticle will greatly enhance optical absorption and, in the presence of a short-pulse ultrasound, induce a discrete cavitation event. The advantage of cavitation here is not to generate bulk heating, but an acoustic emission—which occurs when the bubble collapses. We’ve shown that gold nanoparticles increase the acoustic emission response 100-fold over conventional photoacoustics, enabling much deeper imaging.

bu.edu/eng

Deeper Imaging

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Laser-irradiated nanoparticles can nucleate cavitation activity in the presence of high-intensity focused ultrasound, resulting in a substantial enhancement of acoustic emissions levels.

“Seismic” Drug Discovery

Using the principles of sound, we create nano-earthquakes to mimic blood flow along the surface of microfluidic biochips. These chips could be used in high-throughput experiments to advance more precisely targeted anti-cancer drugs or in a disposable, point-of-care device to test blood samples for thrombosis.

Assistant Professor 38

Matthias Schneider (ME)

Today’s cancer drugs target not only cancerous cells, but many other fast-growing cells throughout the body. As a result, patients undergoing radiation, chemotherapy and other anti-cancer drug regimens suffer from weakened immune systems and other side effects. One strategy to resolve this problem is to design more specialized drugs.

A new acoustics-driven biochip that we developed with collaborators in Austria and Germany will allow us to test these drugs much more efficiently. The chip, which mimics the physical flow conditions of the human body in preclinical tests, could enable scientists to predict and optimize interactions between candidate drugs and target cells more realistically—thereby optimizing delivery to the cancer cells and/or other disease sites.

High-Throughput, Low-Cost Drug Screening The major practical advantage of the SAW chip is its compact size. It uses up to 1000 times less material than conventional flow chambers and can be assembled much faster and inexpensively. Scientists can also use them to test multiple variations of a candidate drug in short order and at low cost. If you mass-produce the chips and deploy them in parallel, you can screen thousands to millions of drugs per day.

We’re now developing a platform of SAW chips that could be used to screen drug candidates in parallel, and a disposable, lab-on-a-chip device that physicians can use to test blood samples for clotting problems and thrombosis.

Microfluidic SAW chips could be used in high-throughput experiments to develop more precisely-targeted anti-cancer drugs. (Source: Lab on a Chip.)

Nanotechnology Research BU College of Engineering

Using surface acoustic waves (SAW) with an amplitude spanning only a few molecules, we pumped a minute amount of liquid containing protein-coated micro- and nanoparticles toward cancerous colon cells on the chip’s surface.

Similar to pumping blood through arteries, the wave created the flow in which the particles were dispersed. We found that particles coated with a bioadhesive protein attached to the targeted cells at a very high rate, whereas those lacking the protein tended to steer clear of the cells.

Sized no bigger than a thumbnail, our microfluidic chip could form the basis of a platform to screen the performance of micro- and nanoparticle-based drug delivery vehicles under a wide range of physiological flow conditions.

bu.edu/eng

Sound-Driven Drug Delivery

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Extracellular Space Exploration

I’m interested in how forces change the shape, or conformation, of proteins that cells use to interrogate their surroundings—fibrous proteins that may ultimately be manipulated to grow desired stem cells or halt the spread of cancer. My main goal is to use advanced tools to investigate the impact of forces on these proteins at the nanoscale level.

Assistant Professor 40

Michael Smith (BME)

To interrogate its surroundings, a cell relies on two-nanometerwide receptors on its surface. These receptors are configured to bind to a fibrous protein matrix in the local microenvironment, but external forces can stretch this fiber, adversely impacting the receptors’ ability to latch onto it. As a result, the cell may miss out on vital information, such as instructions to cancer cells to stop proliferating.

The idea that force can change the cellular environment by altering protein conformation is not new, but tools to demonstrate the mechanism behind this at the receptor level have not emerged until the advent of nanotechnology.

Microfabricated surfaces and a spectroscopic tool can be used to understand protein behavior in a one-micrometer diameter extracellular matrix fiber of fibronectin.

Identifying New Drug Targets Our ultimate goal is to demonstrate conclusively that cells do use force to alter the function of the proteins in their local environment. This could contribute to our mechanistic understanding of tissue development (morphogenesis) and several processes in cancer cell behavior.

By determining whether non-equilibrium protein conformations exist in the local cellular environment and how they contribute to cell signaling, we could develop drug targets against these conformations and new approaches to stem cell-based therapeutics for regenerative medicine and tissue engineering.

Nanotechnology Research BU College of Engineering

The ultimate question is: What is it about protein conformation changes that lead to changed receptor behavior? Probing nonequilibrium binding sites—those perturbed by force—is a novel pharmaceutical concept that requires a new set of tools.

We’re using two nanotech tools: a spectroscopic device called FRET, and an atomic force microscope (AFM). FRET is a nanometer-scale ruler to determine if a protein has been stretched or not. We’ve been adapting this tool for cell culture systems and potentially for ex vivo development models.

The AFM allows us to image the surroundings of the cell at nanometer resolution and detect the cryptic binding sites that get exposed when the protein gets stretched. The device uses an almost single-atom sharp tip to move across the protein’s surface to image precisely where cryptic binding site exposure occurs.

bu.edu/eng

In Search of Stretched Proteins

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Guiding Light We are investigating ways to maximize the amount of light we can extract from carbon nanotubes, and the speed with which we can extract it. Highly efficient light-emitting, semiconducting carbon nanotubes may ultimately advance applications ranging from single-molecule sensing to new light sources.

Associate Professor 42

Anna Swan (ECE) Carbon Nanotube Optics A carbon nanotube is essentially a graphite sheet rolled into a cylinder. Typically extending several micrometers, its diameter is about one nanometer. The electronic structure is effectively onedimensional and depends solely on the direction the graphite sheet is rolled up and the diameter.

Depending on these parameters, the tubes can be either semiconducting or metallic/conducting.

We are interested in the optical properties of carbon nanotubes, since their electronic structure indicates they would be ideal emitters of varying colors. Light is generated by an electron transitioning from an excited energy level to a lower energy level. One promising application for semiconducting carbon nanotubes is single-molecule biosensing.

Nanotechnology Research BU College of Engineering

We are now exploring ways to extract as much light as possible, as quickly as possible, from carbon nanotubes. To achieve that goal, we need to reduce electron diffusion within nanotubes by creating a rugged interior landscape that more efficiently confines the electrons, so they can decay via light emission before they are quenched.

Despite looking like ideal candidates for variable color light emitters, carbon nanotubes originally yielded no light because they were tightly bundled and the electrons dissipated their energy by generating heat instead of light. Back in 2002, people isolated tubes with soap surfactants and started getting light out of them. Instead of starting with bundles and separating individual tubes with soap in solution, we’ve grown tubes in isolated trenches so we can examine the intrinsic properties of each nanotube.

This makes it easier to conduct experiments to improve our understanding of the basics of carbon nanotube light generation—why so little light comes out of the tubes and how to obtain more light at higher efficiencies by limiting light dissipation.

For example, by applying an optical technique called resonant Raman scattering to individual tubes, we are learning more about how changes in the environment impact the tubes’ optical properties. We are also investigating the time evolution of excited electron decay to understand the mechanisms between the competition between light generation and quenching—and how we might Variation of dielectric screening will provide potential design nanotubes to utilize quenching for traps that will localize excited electrons, or excitons, sensors, or avoid it for brighter light sources. yielding higher radiative emission.

bu.edu/eng

Getting the Light Out, Fast

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Pinpoint Detection

We are advancing nanoscale devices in high-resolution imaging of semiconductor circuits for fault isolation, and in high-throughput biological imaging and sensing.

Associate Director of the Center for Nanoscience and Nanobiotechnology 44

Professor

Selim ĂœnlĂź (BME, ECE)

Integrated Circuit Fault Isolation A one-minute delay in developing a new microprocessor chip can cost up to $10,000, and chip manufacturers may have as little as three months to sell their product at a premium.

Finding and resolving defects rapidly is mission critical, but can be challenging.

In the past decade, the basic design scale parameter for semiconductor circuit components has shrunk from about 180 nanometers to 45 nanometers, and the industry roadmap predicts that this figure will reach 11 nanometers in about four years. But the resolution provided by conventional circuit inspection methods began to prove inadequate back at the 180-nanometer level.

In 2000 we developed a subsurface microscopy technique that uses a microlens to image circuits through the substrate, vastly improving imaging resolution over the conventional microscopy method. We have since refined the technique to enable imaging of a 45-nanometer circuit node, and we’ll make further improvements as the industry continues to reduce the design scale parameter size.

Nanotechnology Research BU College of Engineering

We are also developing imaging techniques to probe biomolecular interactions at the sub-nanometer scale in high-throughput sensing applications. One of our label-free platforms, the Spectral Reflectance Imaging Biosensor (SRIB), is 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 can be used to detect proteins, DNA and single viruses. We have already commercialized the technique and applied it to the study of liver disease and Alzheimer’s.

Another platform, spectral self-interference fluorescence microscopy (SSFM), can potentially determine relative changes in molecular orientation with sub-nanometer accuracy—an especially useful capability in probing DNA-protein interactions. We apply an electric field to orient the DNA molecules in a well-ordered manner so that when we introduce a protein in solution, the protein will bind to the DNA and change its shape, resulting in a change in the spectral signature we observe from fluorescent molecules attached to the DNA. We can then detect the spectral signature change and attribute that to a conformational change.

Our goal is to use SSFM to analyze different protein-DNA interactions and to identify and characterize specific proteins that induce considerable shape changes in DNA molecules that may contribute to the onset of certain diseases.

bu.edu/eng

Biomolecular Interaction Detection

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Lilliputian Scouts

We are developing iron oxide nanoparticles as a material to help engineers find oil in the ground, and as imaging contrast agents to facilitate the early detection of heart disease.

Associate Professor 46

Joyce Wong (BME) Oil Detection As much as 70 to 80 percent of oil gets left behind in existing wells, so to recover a fraction of that would make a huge impact. We’re using a 20-nanometer-diameter iron oxide nanoparticle core to help inform oil explorers on the environment inside the well. The nanoparticles are little reporters with the potential to tell you more information about the properties of what they encounter.

Our goal is to inject nanoparticles at the top of the bore hole, and receive signals from them that collectively provide a profile of what they encounter. Working with Linda Doerrer [assistant professor of chemistry at Boston University] and Igal Szleifer at Northwestern University, we are using MRI to read the signals, which can then be analyzed to determine if oil is present.

We ultimately aim to develop a field-testing tool to enable oil explorers to determine where additional oil may be extracted. Working with experimental packed-sand models, By adding a marker to iron oxide particles, Wong hopes to develop our immediate goal is to make sure the particles don’t stick a noninvasive method for to the sand and minerals further down a bore hole, and to differentiating between stable and unstable arterial plaques in MRIs. demonstrate this computationally.

bu.edu/eng

Vulnerable plaques are unstable structures in an arterial wall that could rupture in minutes to hours, leading to stroke, heart attack or pulmonary embolism.

Our goal is to develop magnetic resonance contrast agents—using the same 20-nanometer-diameter iron oxide nanoparticles—to detect vulnerable plaques before they rupture. Aided by these nanoparticles, a physician could determine whether a plaque is likely to rupture and needs immediate treatment.

One of my collaborators, James Hamilton, professor of physiology and biophysics at the Boston University School of Medicine and an affiliated faculty member in our biomedical engineering department, developed a unique animal model for the study of triggered plaque rupture—a model that closely resembles the progression of disease in humans. By injecting imageenhancing nanoparticles into the arteries in these regions, physicians could examine plaques and determine potential rupture sites.

Based on our research, we envision a noninvasive, diagnostic kit that a doctor could use to determine if a patient needs treatment for vulnerable plaques and subsequently monitor that treatment.

Nanotechnology Research BU College of Engineering

Heart Disease Detection

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Frontiers of Nanomedicine Drawing on lessons from materials science and engineering, we’re developing nanoscale devices to provide enhanced observation of critical processes within living cells, enhanced, in vivo imaging of complex biological environments, and ultrasensitive detection of gases and photons. Our research could lead to high-throughput drug development, more accurate disease diagnosis and improved environmental monitoring.

Associate Professor 48

Xin Zhang (ME, MSE)

Probing Subcellular Forces To improve our understanding of the behavior of living cells at the subcellular level, we’re pursuing two projects that use nanodevices to study cellular forces in muscle, cardiovascular and stem cells.

To observe small forces within cells, we take both mechanical and electrical measurements. For instance, we are using a biomechanical sensor to observe living cardiovascular cell contraction. We have developed a polymer-based system allowing for a simple way to measure accurately and repeatedly the mechanical forces in multiple contracting cells, and yet retain all the capabilities of standard molecular biology manipulation.

We have also developed an electrical biosensing technique for detecting cellular responses utilizing real-time monitoring of cell adhesion with impedance spectroscopy. We have demonstrated the technique in detecting ongoing cell death processes in cardiac muscle cells, and plan to scale it up to Copper oxide nanowires’ brush-like perform high-throughput biosensing for cell biology and structure enables high-resolution pharmacology applications. detection of gases and photons.

bu.edu/eng

In the imaging and photonics area, we are designing a novel type of nanoparticulate contrast agent that could enable multi-spectral and functional imaging capabilities in MRI applications.

Combining the multiplexing capabilities of labeling technologies in optical imaging and the in vivo imaging capability of MRI, our biocompatible magnetic iron oxide nanoparticles could facilitate in vivo imaging of complex biological environments with myriad biomedical applications.

The particle geometry yields distinct spectral properties and allows for diffusion of water through the particle, yielding orders of magnitude signal amplification compared to currently available contrast agents. Our functional MRI contrast agent could also yield more accurate diagnosis and characterization of pathologies ranging from cancer to artherosclerosis.

Finally, we are developing miniature sensors with copper oxide nanowires, which have a brush-like structure that facilitates high-resolution detection of trace amounts of gases and photons. Our preliminary results show that this sensor is highly sensitive to carbon monoxide and other gases. Copper oxide is a very new material for nanowires that’s cheap and easy to manipulate and package into a micro-template targeting gas and photon sensing. Our template could be used for environmental monitoring, medical diagnosis and lab-on-a-chip analytical devices.

Nanotechnology Research BU College of Engineering

Enhancing Imaging and Detection Capabilities

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RESEARCH CENTERS AND ACADEMIC PROGRAMS Center for Nanoscience and Nanobiotechnology nanoscience.bu.edu By combining advances in nanoscale materials and platforms with biomedical engineering to understand subcellular processes, biomolecular function and human physiology, the Center for Nanoscience and Nanobiotechnology (CNN) is accelerating technological innovations at the forefront of nanomedicine and nanophotonics, impacting human disease, bio-threat detection and energy research.

To cultivate collaborative scientific advancement at the nanoscale, CNN integrates Boston University’s interdisciplinary efforts in materials science, surface science, physics, chemistry, engineering, molecular and cellular biology, biophysics, microfluidics, MEMS and manufacturing through seminars, meetings, joint visitor programs, interdisciplinary courses, industrial collaborations and seeded projects. Toward that end, the Center recently launched a large-scale Nanomedicine Initiative, coupling 25 faculty researchers from the Charles River and Medical Campuses.

Photonics Center bu.edu/photonics

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The Boston University Photonics Center (BUPC) builds strong academic programs in the science and engineering of light, and develops advanced photonic device prototypes for commercial and military applications. Groundbreaking research conducted at the center includes work on science and technology for solidstate source and detector materials, quantum cryptography, subsurface imaging, adaptive optics, micro-optoelectromechanical systems, high-speed modulation and sensing, bioorganic chemistry, nanophotonic devices and biomedical applications of photonics.

Occupying 235,000 square feet on ten floors, the BUPC houses more than 25 faculty research laboratories; three shared laboratories focused on optoelectronic processing, integrated optics and precision measurement; a business incubator; and instructional and seminar facilities specifically designed for photonics research and education.

Undergraduate Nanotechnology Concentration bu.edu/eng/ugrad/concentrations/nano Launched in September, 2009, the College of Engineering’s Nanotechnology concentration provides undergraduate engineering students with foundational knowledge of the manipulation of matter at the molecular and atomic scale, and positions them for future careers in the nanotechnology field. Students focus on the emergence of nanotechnology and its effects on biomedical, photonic, electronic and atomic systems.

The required courses for the 16-credit concentration provide an introduction to nanotechnology and examine how engineering works on scales as small as billionths of a meter. Students explore the foundations of quantum mechanics, atomic structure and the physics of molecules and solids. The multidisciplinary elective courses include different approaches to biomedical engineering on the cellular and sub-cellular level; behavior of materials at atomic levels; micro-electrical mechanical devices and systems (MEMS); and photonics and fiberoptic communication.

Nanotechnology Graduate Fellowships Of the many fellowship programs that support College of Engineering graduate students, three target students who seek to pursue coursework and research in nanotechnology.

• GAANN: Funded by the Department of Education’s Graduate Assistance in Areas of National Need (GAANN) Program, the GAANN fellowships are offered to outstanding biomedical engineering or electrical and computer engineering PhD students who wish to focus on nanobiotechnology. Fellows receive a generous stipend for one to two years to pursue academic studies and research in the field, which is well-represented at the Boston University Center for Nanoscience and Nanobiotechnology. GAANNfunded students develop teaching skills through mentored classroom and laboratory teaching assignments; independent research abilities through interdisciplinary classes and faculty-directed research activities; and training in the technology transfer and commercialization of nanobiotechnology.

• TRB: Funded by the National Institutes of Health (NIH) to improve prospects for biomaterials solutions for tissue engineering and drug delivery, the five-year Translational Research in Biomaterials (TRB) fellowships are offered to biomedical engineering PhD students. The TRB program seeks not only to train doctoral students in scientific aspects of biomaterials, but also to provide them with a solid understanding of clinical trials, commercialization strategies and other concepts needed to effectively transition research ideas from the laboratory to the clinic. Key program components include quantitative science and engineering courses; interdisciplinary laboratory research modules; a student-organized journal club; translational training in clinical trials, business and ethics; clinical trial experiences; and industrial internships.

• CIMIT: The Center for Integration of Medicine and Innovative Technology (CIMIT) selects five Boston University College of Engineering doctoral students each year for its Applied Healthcare Engineering Fellowship awards. A nonprofit consortium of Boston teaching hospitals and engineering schools (including the BU College of Engineering), CIMIT seeks to rapidly improve patient care by facilitating interdisciplinary collaboration among leading experts in medicine, science and engineering. Covering students’ tuition, stipend and some ancillary expenses, CIMIT fellowships support highly innovative yet traditionally underfunded areas of healthcare research, including medical device development, new algorithms and software for use in clinical practices, and innovative engineering of medical environments.

Division of Materials Science and Engineering bu.edu/mse An interdisciplinary field, materials science and engineering is driving innovations in biomaterials, electronic and photonic materials, materials for energy and environment and nanomaterials applications. Solid-state lighting and fuel cells are but two examples of exciting current materials research activities at Boston University that are likely to fundamentally impact life in the 21st century. Applications for new materials, and modifications of existing ones, are expected to keep the demand for trained, graduate-level materials scientists and engineers growing in large companies, startups and academia.

Nanomedicine Initiative nanoscience.bu.edu/nanomedicine A joint program of the Boston University Center for Nanoscience and Nanobiotechnology (CNN), the Department of Medicine, the Evans Center for Interdisciplinary Biomedical Research, the Office of the Provost, the Dean of Engineering and the Dean of Arts and Sciences, the Nanomedicine Initiative seeds collaborative efforts in basic science and discovery in nanomedicine. The program seeks to support new collaborations in innovative applications of nanotechnology to medicine. Its ultimate goal is to enable researchers to test new ideas, build interdisciplinary teams and generate the preliminary data necessary for successful applications to external funding agencies.

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bu.edu/eng Professor Xin Zhang (ME, MSE) observes cellular forces by placing individual cells atop arrays of nanoscale pillars made of soft polymers.