healthcare technology brochure

HEALTHCARE TECHNOLOGY

RESEARCH

Saving Lives,Cutting Costs

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ENGINEERING HEALTHCAREFrom drug-coated stents that keep hearts beating to ultrafast CT scans that catchtumors early, high-tech innovations are enabling dramatic improvements in thequality of healthcare across the globe. Deployed correctly, advanced medicaltechnology not only improves health outcomes but also makes healthcare moreaffordable in both developed and resource-limited countries. For example, a label-free, chip-scale, point-of-care biosensor could enable medical personnel to diagnoseinfectious diseases rapidly on-site, avoiding expensive, centralized lab processingand delays in treatment.

This is but one of dozens of higher-quality, lower-cost healthcare solutionsemerging from Boston University’s College of Engineering. Others include faster,cheaper DNA sequencing that could revolutionize personalized medicine; targetedcancer treatments designed to minimize potentially lethal side effects andtreatment time; new devices to detect and monitor cardiovascular diseasenoninvasively; and sophisticated biomaterials for bone healing and injury repair.

A Multi-Disciplinary, Multi-Scale EndeavorAnchored by its top-10-ranked Biomedical Engineering department, BU College ofEngineering healthcare technology research often involves collaborations that spanmultiple departments and divisions and leverage the expertise of physicians andmedical researchers from the BU School of Medicine, the BU Goldman School ofDental Medicine and other Boston-area medical research institutions. Projects arefunded by major federal agencies such as the National Institutes of Health, NationalScience Foundation, and Department of Defense, as well as by private foundationssuch as the Wallace H. Coulter Foundation.

In their efforts to advance our fundamental understanding of biology andphysiology in health and disease and translate these principles into highly effectiveand affordable clinical technologies, our researchers are not only crossingdepartmental boundaries, but also working at every scale of biology—from moleculeto cell to tissue to patient.

Saving Lives and MoneyWhether designed to prevent, diagnose, treat ormanage disease, healthcare technologiesemerging from the BU College of Engineeringpromise to improve patients’ well-being,saving them money, and, quite possibly,their lives. As you’ll see on the followingpages, our researchers are facing—andovercoming—formidable challenges todeliver on that promise.

Saving Lives, Cutting Costs BU College of Engineering2

RESEARCH AT-A-GLANCE

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Lighting the WayOn-Chip Pathogen Detection with PlasmonicsAssistant ProfessorHatice Altug (ECE, MSE)

High-Res Checkup Tracking Single Molecules in CellsAssistant Professor Sean Andersson (ME)

Beyond the Eye Chart Tracking Retinal Disease with Adaptive OpticsProfessor Thomas Bifano (ME, MSE); Director of the Boston University Photonics Center

Hybrid BiosensorsCombining Optical Nanostructures and Silicon Technologyfor Pathogen DetectionAssociate Professor Luca Dal Negro (ECE, MSE)

8Managing Obesity Boosting Immune Response, Reducing ComplicationsAssociate Professor Calin Belta (ME, SE)

10 Scattered LightNoninvasive, Early Cancer DetectionProfessor Irving Bigio (BME)

11 Making the Medicine WorkTargeting Recurring Bacterial Infections with Sugar-Coated AntibioticsProfessor James Collins (BME, MSE, SE)

13 Closing the LoopA Bionic Pancreas for Low-Maintenance DiabetesProfessor Edward Damiano (BME)

14 BrainteaserSystems Biology Platform Helps Pinpoint GeneticPredisposition for GliomaProfessor Charles DeLisi (BME); Dean Emeritus, College of Engineering

15 Reconfigurable BiologySynthetic Biology Tools Probe DNA “Circuitry” Behind TBAssistant Professor Douglas Densmore (ECE)

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20Nipped in the BudTargeted Chemotherapy for Lung Cancer PatientsProfessor Mark Grinstaff (BME, MSE)

23No Needles, PleaseAn Electrostatic Method for Pain-Free InoculationProfessor Mark Horenstein (ECE)

16 Exotic and DeadlyMonitoring Potentially Malignant Rare CellsResearch Professor Daniel Ehrlich (BME)

18 A First Responder’s DreamPortable, Noninvasive Imaging of Brain InjuriesLecturer Caleb Farny (ME)

19 Deconstructing TBHoning in on Potential Drug TargetsAssociate Professor James Galagan (BME)

21Mind AlteringOptical Neurotechnologies to Probe and Correct Brain DisordersProfessor Xue Han (BME)

22Catching the WaveA Faster, Cheaper Way to Grow TissueAssociate Professor Glynn Holt (ME)

17 No Swimming AllowedNanoscale Diving Boards that Detect PathogensAssociate Professor Kamil Ekinci (ME, MSE)

24Sharper ImageA Blur-Free Scanning Method for Improved Heart MonitoringProfessor W. Clem Karl (ECE, SE)

25Tipping PointsLung Cancer Biomarkers Present New Drug TargetsProfessor Simon Kasif (BME)


36Going with the FlowSound Wave-Driven, Microfluidic Biochips for Cancer Drug DiscoveryAssistant Professor Matthias Schneider (ME)

35At the Turn of a DialNanoparticle-Assisted Ultrasound for Tumor Imaging and TherapyProfessor Ronald Roy (ME); Chair, Department of Mechanical Engineering

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Of Lasers and LEDsFighting Pathogens with UV TechnologyProfessor Theodore Moustakas (ECE, MSE)

Sounding Out TumorsUltrasound Techniques for Targeted Cancer Drug DeliveryAssistant Professor Tyrone Porter (ME)

30Look InsideLow-Cost, High-Res, Deep Imaging of Bodily OrgansAssociate Professor Jerome Mertz (BME)

31All in the CartilageImaging Diagnostics for Bone Fracture HealingAssociate Professor Elise Morgan (ME, MSE)

33Data-DrivenAlgorithms for Better, Cheaper HealthcareProfessor Ioannis Paschalidis (ECE, SE)

29The $100 GenomeFaster, Better, Cheaper Personalized MedicineProfessor Amit Meller (BME, MSE)

28Getting the Right DoseEngineering More Effective Drugs for Lung Disease Research Professor Malay Mazumder (ECE)

26Point-of-CareInfectious Disease Diagnostics on a Chip Associate Professor Catherine Klapperich (BME, MSE)

27Tree WorkProbing the Lung’s Branching Airways to Improve Asthma Treatment Professor Kenneth R. Lutchen (BME); Dean, College of Engineering

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Color-CodedPrecisely Engineered Magnetic Resonance Imaging (MRI)Contrast Agents Using a Top-Down ApproachProfessor Xin Zhang (ME, MSE)

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Shape MattersA New Pathway to Anti-Cancer Drugs and Tissue EngineeringAssistant Professor Michael Smith (BME)

High ContrastNanoparticle-Enhanced Imaging for Heart Disease Detection Associate Professor Joyce Wong (BME, MSE)

37Vaccines On-DemandHigh-Production Factory Extracts Medicines from Tobacco PlantsProfessor Andre Sharon (ME)

38Can you Repeat That?Advancing Better Hearing Diagnostics and AidsProfessor Barbara Shinn-Cunningham (BME)

College of Engineering faculty affiliations that appear in this brochure include home departments—Biomedical Engineering (BME), Electrical Engineering & Computer Science (ECE) and MechanicalEngineering (ME), and divisions—Materials Science & Engineering (MSE) and Systems Engineering (SE).

43Missed SignalsFinding New Cancer Drug Targets Where Proteins Combine Professor Sandor Vajda (BME, SE)

45Simple, Cheap and DurableMedical Technologies for Resource-Limited Countries Associate Professor Muhammad Zaman (BME)

46Breaking Down the WallsBiomechanical Model to Probe Cardiovascular DiseaseMechanisms and Potential Therapies Assistant Professor Katherine Yanhang Zhang (ME, MSE)

42Label-FreeOn-Chip Pathogen Detection with Interferometry Professor Selim Ünlü (ECE, MSE)

40Breathing FreeNew and Improved Mechanical VentilatorsProfessor Bela Suki (BME)

41Lifelines, LiterallyEngineered Blood Vessels for Reconstructive SurgeryAssociateProfessor Joe Tien (BME)

LIGHTING THE WAYOn-Chip Pathogen Detection with Plasmonics

Assistant Professor HATICE ALTUG (ECE, MSE)

Rapid, chip-scale, low-costdetection of viruses and otherpathogens is critical intreating infectious diseasesand curbing the spread ofpandemics, but today’sbiodetection technology fallsshort. Most diagnostic testsfor bacterial and viraldiseases are too expensive,time- and labor-intensive tobe completed at point of care,leading many physicians tooverprescribe antibiotics andmiss opportunities to containviral outbreaks.

But Assistant ProfessorHatice Altug (ECE, MSE) hasintroduced an opticalbiosensor platform that couldchange all that. Developed incollaboration with BostonUniversity School of Medicine

When a live virus (blue) binds to an immobilized antibody (green) on the sensorsurface, the effective refractive index in the close vicinity of the sensor changes,causing a detectable shift in the resonance frequency of the light transmittedthrough the nanoholes.

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We’re developing alabel-free, real-time,multiplexed detectionsystem withunprecedented sensingcapabilities. This lab-on-a-chip platformcould be used in point-of-care diseasediagnostics and drugdiscovery applications.

microbiologist John Connor,this highly sensitive, on-chipbiosensor rapidly detects liveviruses from biological mediawith minimal samplepreparation.

It’s the first to detect intactviruses by exploitingplasmonic nanohole arrays—250-350 nanometer-wideapertures on metallic filmsthat transmit light morestrongly at certainwavelengths. When a livevirus binds to the sensorsurface, it triggers adetectable shift in theresonance frequency of thelight transmitted through thenanoholes. The magnitude ofthat shift reveals the presenceand concentration of the virusin the solution.

Two well-known biological imaging techniques—atomicforce microscopy (AFM) and confocal fluorescencemicroscopy (CFM)—use a point-like sensor which movesback and forth in a raster scan, sampling point-by-pointto build an image, pixel-by-pixel. The techniques performwell in capturing static phenomena, but are far too slowto image dynamic biological processes.

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Custom-built tracking confocal microscope. By actuating the relativeposition of the focal point of the microscope and the sample (achieved hereby moving the sample with a nanopositioning stage), a single fluorescingmolecule is followed over seconds to minutes. This approach allows forexisting single molecule techniques to be applied over a much broader timerange, thereby providing significantly more information, as well as a directapproach to understand the motion of that molecule.

Now Assistant Professor SeanAndersson (ME, SE) is reconfiguringAFM and CFM with new softwarealgorithms to perform high-speed,high-resolution dynamic imaging inorder to track the behavior of singlemolecules in solution, and, eventually,living cells.

To accelerate AFM, Anderssonfocuses only on dynamic processesoccurring along string-like biopolymers.Using AFM measurements ofbiomolecules to direct the instrument’ssharp tip close to the string, he’sminimizing data collection and timeneeded to build an image. To accelerateCFM and effectively obtain a wide fieldof view of a dynamic process,Andersson moves the instrument’sdetection volume through a feedbackprocess. Based on the measurementshe gets from the fluorescence of what’smoving, he advances the detectionvolume to follow the action.

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Assistant Professor SEAN ANDERSSON (ME, SE)

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Our research centers on developing and applyingnew instrumentation for studying dynamics insystems with nanoscale features, especially proteinsand other biomolecules. These tools could helpimprove our understanding of biological processesat the molecular level and lead to new insights andeven new treatments for a variety of cardiac, brain,neuroinflammatory and other disorders related tochanges in the dynamics at this scale.

HIGH-RES CHECKUPTracking Single Molecules in Cells

MANAGING OBESITYBoosting Immune Response, Reducing Complications

Associate Professor CALIN BELTA (ME, SE)

Experiments by Boston UniversityGoldman School of Dental MedicineProfessor Salomon Amar indicate thatobese organisms have a deficientimmune response to infection, leadingto significantly longer-lastingillnesses. To better understand howbody mass index impacts the immuneresponse—and to try to reverse theprocess, Amar is collaborating with anexpert in computational modeling ofgene and other networks, AssociateProfessor Calin Belta (ME, SE).

Amar and Belta are developing agenome-scale mathematical model ofmetabolism, signaling and genenetworks in the immune system cellsof lean and fat strains of mice infectedwith the microorganism P. gingivalis.The researchers obtain gene

Macrophages from lean andobese mice are exposed to P.gingivalis infection. Thecorresponding geneexpression data is fed intothe researchers’computational tools topredict genes that areessential to this response.

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Our goal is todetermine howobesity affects theresponse toinfection—knowledge thatcould be used todevelop targeteddiagnostics anddrugs for infectionsin obese patients.

expression data,computationallypredict which genesare restricting theimmune response,and knock out orover-express thosegenes to see if theyprovoke sharpdifferences inimmune response inthe two strains.

The effort couldlead to a medicationrendering obeseindividuals less proneto infectious diseasesand better equippedto mount an effectiveimmune response,thereby reducing thecomplications andcosts—about $150billion annually in theU.S.—of obesity.

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Developed at Boston Universityover the past decade, ProfessorThomas Bifano’s (ME, MSE)deformable mirrors are widelyused to compensate for opticalaberrations in telescopes andmicroscopes. His “adaptiveoptics” technique uses MEMStechnology—electrostaticactuators and flexible layers ofsilicon—to shape the mirrorsprecisely and to bring images ofeverything from cells to planetsinto sharper focus. And nowthe technique has found its wayinto the clinic.

A research consortium hasproduced a prototype of ascanning laser ophthalmoscope(SLO) that uses Bifano’sdeformable mirrors tocompensate for optical

Photograph of MEMS Deformable Mirror usedin the new ophthalmoscope. The 4mm squaremirror membrane can be reshaped using anunderlying array of 140 actuators tocompensate for optical imperfections in theeye, allowing sharper retinal images.

Professor THOMAS BIFANO(ME, MSE)Director, Boston UniversityPhotonics Center

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With colleagues fromIndiana University andBoston MicromachinesCorporation, I developed ahigh-resolution retinalimaging system. Used byJoslin Diabetes Centerresearchers to studymolecular mechanisms ofretinal disease indiabetes, this instrumentprovides the highestresolution ever attained ina clinical setting, andenables the first directimaging of cell-sizedstructures in the retinas ofpatients with eye disease.

aberrations of the eye,yielding cell-scale, in vivoimages of the retina.Clinicians at the JoslinDiabetes Center are expectedto use the integrated SLO tostudy the progression ofselected diabetes-relatedretinal diseases and to assess the effectiveness ofclinical treatments.

The technology mayultimately enhance routineeye exams. “Upon detectingsigns of an abnormality usinglow-resolution diagnostics,an ophthalmologist could use this instrument to obtainvery high-resolution scansover the entire retina, and totrack disease progression,”says Bifano.

High resolution image of aportion of the retina made atJoslin Diabetes Center with theophthalmoscope. Conephotoreceptor cells are clearlyresolved, as is blood flowthrough traversing vessels.Imaging these structures invivo will advance the study ofeye disease.

BEYOND THE EYE CHARTTracking Retinal Disease with Adaptive Optics

SCATTERED LIGHTNoninvasive, Early Cancer Detection

Professor IRVING J. BIGIO (BME)

In the 1990s, Professor Irving J.Bigio (BME) pioneered anoninvasive early cancerdetection method called elasticscattering spectroscopy (ESS),in which a fiber-optic probe ispassed through an endoscopeor catheter, or integrated into asurgical tool. When the probe’stip is in gentle contact with thetissue, an optical fiber shineswhite light into the tissue, andan adjacent optical fibercollects light scattered backfrom the tissue. Software thenanalyzes the spectrumscattered from the tissue with astored diagnostic algorithm topinpoint early signs of cancer.

Based on clinical studieswith hundreds of patients, ESSshows great promise as a low-cost, low-maintenance,user-friendly clinical tool fordiagnosing early stage colon,esophageal and other holloworgan cancers, but recentresearch shows that themethod could also providetimely, critical information tocancer surgeons.

Optical fibers integrated into the biopsy forceps used during colonoscopy can shinelight on the tissue, and the ESS system can provide instantaneous diagnosticinformation to the endoscopist about the risk potential of the tissue.

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”We’ve developed an optical method to detect sub-cellular structural changes in the epithelial layer ofhollow organs associated with pre-cancer conditionsor the onset of cancer. The method could be used notonly in noninvasive diagnosis of selected early stagecancers, but also in guided cancer treatment.

One example is to assess the resection margins during breastcancer surgery, to assure that no cancer is left behind. Anotherexample, in collaboration with Boston University School ofMedicine specialists, is the clinical testing of a new device thatintegrates ESS into the fine needle aspiration diagnostic tooltypically used to probe the thyroid gland. Delivering additionaldiagnostic information, the enhanced tool could prevent manyunnecessary thyroidectomies.

MAKING THE MEDICINE WORKTargeting Recurring Bacterial Infections with Sugar-Coated Antibiotics

ProfessorJAMES COLLINS (BME, MSE, SE)

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antibiotics such as gentamicin. Asugar-antibiotics combination couldbe used to obliterate recurring,often debilitating infections such asthose of the ear, throat, lungs andurinary tract, all of which canspread to the kidneys and othervital organs if left unchecked.

Collins and Allison are nowinvestigating the impact of sugaradditives on the efficacy of drugsfor tuberculosis, which killsapproximately two million peopleworldwide each year.

“ ”Adding certain sugars to first-lineantibiotics can dramatically boosttheir effectiveness, and may lead tobetter treatments for recurringbacterial infections and TB.

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A discovery by Professor James Collins(BME, MSE, SE) and PhD student KyleAllison (BME’11) may deliver a newweapon in the daunting battle againstrecurring, potentially lethal bacterialinfections such as staphylococcus andstreptococcus. And the weapon—a modifiedform of sugar—is as widely available andcheap as it is effective, says Collins.

“A spoonful of sugar makes themedicine work,” says the MacArthurgenius award recipient. It does that, hesays, by “waking up” stealthy, dormantbacteria that can lie in a state of metabolichibernation for weeks or months.

The researchers found that sugardramatically boosts theeffectiveness offirst-line

HYBRID BIOSENSORSCombining Optical Nanostructures and Silicon Technology for Pathogen Detection

Associate Professor LUCA DAL NEGRO(ECE, MSE)

Using precisely-engineeredarrays of metallic and siliconnanoparticles to boost theintensity of optical fieldslocalized on two-dimensionalsurfaces, Associate ProfessorLuca Dal Negro (ECE, MSE) isdeveloping a new platform fornanoscale optical sensing thatcould be used to detectdisease-causing pathogenswith superior accuracy and dependability.

“We envision optics andelectronics components onhigh-density silicon chips on asilicon-based materialsplatform,” says Dal Negro. “Thisleads to inexpensive, high-performing, mass-producible,electrical and optical deviceswith superior performancesresulting from engineeredelectric fields at the nanoscale.

Figure shows (a) white light microscope image of anaperiodic surface of gold nanoparticles; (b) electronmicroscope picture of fabricated arrays of gold nanoparticleson silicon (the pattern shows detail of aperiodic two-dimensional surface); (c) white light microscope image of anaperiodic spiral of gold nanoparticles on silicon; and (d)electromagnetic simulation of a localized optical wavetrapped on the two dimensional surface referenced in (b).

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We’re developingefficient, nanoscale,metallic andsemiconductingnanoparticles on planarsilicon-based chips forthe engineering ofsuperior light sources,optical sensors andlaser structuresboosted by opticalfields confined at thenanoscale. Ourresearch could result innovel and moresensitive opticalbiosensors fullyintegrated withwidespread silicontechnology.

This vision can enable aninexpensive, integrated siliconchip with thousands ofwaveguides, modulators,detectors and other opticalcomponents interacting withcontrollable nanoscale fields,all within the standardmicroelectronics circuitry.”

By engineering the shapeand size and arrangement ofnanoparticles to scatter lighton two-dimensional surfaces,Dal Negro aims to boost theperformance of current opticalbiosensors, photo-detectorsand other active photonicdevices. Potential applicationsinclude biosensors capable ofdetecting harmful bacteria,viruses and food and watercontaminants with greaterreliability and lower error ratesthan current technology.

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Working with endocrinologistsSteven Russell and DavidNathan at MassachusettsGeneral Hospital (MGH),Associate Professor EdwardDamiano and Senior ResearchAssociate Firas El-Khatib(both BME) have conductedsuccessful clinical trials atMGH in adults and childrenwith type 1 diabetes, testingprototypes of the bionicendocrine pancreas that theydeveloped. Aimed at peoplewith type 1 diabetes who mustmonitor their blood glucoselevels throughout the day andcontinuously receive insulin,the system uses automateddecision-making software topump insulin (a blood-glucoselowering hormone) andglucagon (a blood-glucose

In an ongoing clinical trial at MGH, adults and children with type 1 diabetes areconnected to an experimental version of the software-controlled, automated bionicpancreas for 51 hours and provided with six carbohydrate-rich meals. The systemresponds to glucose readings streamed online every five minutes from a continuousglucose monitor, and commands insulin and glucagon doses wirelessly usinginfusion pumps. Intravenous blood glucose is also monitored every 15 minutes totest the system, but this information is not provided to the bionic pancreas.

Professor EDWARD DAMIANO(BME)

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We’re developing asoftware-controlled,bionic endocrinepancreas to enablepeople living with type 1diabetes to maintainmuch safer and betterblood glucose controlwith far less effort thancan be achieved withconventional therapies.

CLOSING THE LOOPA Bionic Pancreas for Low-Maintenance Diabetes

raising hormone) just belowthe skin using FDA-approvedinfusion pumps based onmeasurements obtainedevery five minutes from acommercially availablecontinuous glucose monitor.

The device emulates theendocrine pancreas, whichcontinually secretes thesetwo hormones to regulateblood glucose.

“Our automated systemwill not only reduce thedecision-making burden onpeople with type 1 diabetesand their caregivers, but willalso keep blood glucoselevels within a muchhealthier range than what’sachievable for most peoplewith today’s therapies,” says Damiano.


OUT OF FOCUS

BRAINTEASERSystems Biology Platform Helps Pinpoint Genetic Predisposition for Glioma

Professor CHARLES DELISI (BME)Dean Emeritus, College of Engineering

Depending on its location, a high-grade gliomacan cause seizures, vision loss, numbness or othersymptoms. This relatively uncommon disease,which tends to arise between the ages of 45 and70 and caused the death of the late SenatorEdward M. Kennedy, is rarely curable, but researchby Professor Charlers DeLisi (BME) could lead tonew therapies designed to prevent its onset.

Using a large systems biology platform he andcolleagues developed over the past decade to mapthe relationships among cellular networks ofgenes and proteins involved in cancer and other

“ ”We have identified 29 genes thatpredispose to glioma, a tumortypically found in the brain, opticnerve or spinal cord. Some of thesegenes could serve as drug targets.

biological processes, DeLisi and Department ofMathematics & Statistics Professor Mark Konand postdoctoral fellow Tun-Hsiang Yangconducted a study to identify geneticpredispositions.

“We used blood cells from a group of peoplewith and without glioma, and compared up toone million sites in their genomes,” says DeLisi.“As a result, we identified 29 genes unique toindividuals with the disease, 12 of which arealready known to be cancer related. Some ofthe 29 could be potential drug targets.”

Regions on chromosomes 1 and 9 that contain some of the cancer related genes that appear to predispose to glioma. For example,CDKN2 is known to regulate cell division; its loss diminishes growth regulation and predisposes to cancer.

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Reconfigurable circuits are designed using computer software and then introducedinto bacteria. These circuits then “reconfigure” themselves with the introduction ofspecific enzymes into configurations to test gene interaction.

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RECONFIGURABLE BIOLOGYSynthetic Biology Tools Probe DNA “Circuitry” Behind TB

Assistant Professor DOUGLAS DENSMORE

(ECE)

Assistant Professor DouglasDensmore’s (ECE) researchfocuses on the development oftools for the specification, designand assembly of syntheticbiological systems, which can beused to model how naturalbiological systems function. He’scurrently applying these tools tohelp accelerate AssociateProfessor James Galagan’s(BME) efforts (see p. 19) toreverse engineer the process bywhich selected genes turn onand off in “circuits” (collectionsof DNA segments) withinMycobacterium tuberculosis andthereby enable the bacterium tobecome pathogenic.

“Our software lets you make areconfigurable DNA circuit—

producing it once andreconfiguring it for multipleexperiments, either incomputer simulations or inthe lab,” says Densmore. “Byisolating genes suspected oftransforming the TBbacterium to a pathogenicstate and studying theirinteractions, we hope tobetter understand thisprocess and how to inhibit it.”

There’s a pressing need toget a handle on this process:Approximately one-third ofthe world’s population isinfected with TB (about 1.7million died from the diseasein 2009), and the threat frommulti-drug resistant strains is growing. “

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Using computationaltools, we can createsynthetic genenetworks—collections ofengineered DNAsegments—which can bereconfigured to examinehow bacterial systemsdevelop. We are applyingthese tools to supportAssociate ProfessorJames Galagan’s (BME)efforts to model generegulatory networks inthe bacterium thatcauses tuberculosis, andthereby uncover newdrug targets.

EXOTIC AND DEADLYMonitoring Potentially Malignant Rare Cells

Research Professor DANIEL EHRLICH(BME)

An emerging view likenscancer to contagious disease.Under the body’s systemiccontrol or ongoing drugtreatment, a balance ismaintained between healthyand potentially malignant rarecell types, such as earlycancer cells. It is when thesecells proliferate and subvertthis balance that diseaseemerges. To monitor thedevelopment of rare cellswould require molecular-leveldetection capability, butcurrent genomics technologyprovides too blunt aninstrument.

Research Professor DanielEhrlich (BME) is nowassembling a more preciserare cell detection technology

Microfluidic devices used for high-content cell cytometry. A 16-test disposable devicefor clinical applications and a larger 384-channel device, suitable for high-throughputdrug development, are shown. A typical cytometry trace is shown on right.

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Our laboratory isdeveloping the newmethods andinstruments needed togather detailedmolecular snapshotsfrom rare cells that cantrigger cancer and otherdiseases—for both drugdevelopment andclinical diagnosis.

that combines elements ofhigh-speed microscopy (toimage cells at the molecularlevel) and flow cytometry (toanalyze cells suspended in astream of fluid). The newtechnology enables high-throughput detection andanalysis of the cells, greatlyexpanding the number ofsamples that can beinvestigated per unit time.

“We’re building a second-generation prototype of whatwe call a parallel microfluidicscytometer,” says Ehrlich. “It’s adisposable, plastic cartridgethat automates the standardinstrument lab techs use toanalyze blood samples, and canalso be adapted for high-throughput drug discovery.”

What is a Parallel Microfluidic Cytometer (PMC)?

When a pathogenattaches to one ofAssociate ProfessorKamil Ekinci’s (ME, MSE)vibrating, nanoscalediving boards, the boardbecomes heavier and itsresonant frequencydecreases. By bouncinglight or radio waves offthese boards, one canmeasure this reducedfrequency and detect the pathogen.

After showing that thediving boards worked in avacuum and in air,Ekinci’s next challengewas to enable them todetect a biomolecule in afluid such as a bloodsample—all whilepreventing the fluid fromsticking to the board anddampening its vibrationalmotion. He subsequently

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Ekinci’s lab is developing diving-board-like cantilevers to detect trace amounts of pathogensin water. The textured surfaces are designed to overcome water’s inherent stickiness, whichinhibits the devices’ sensitivity.

designed super-hydrophobic structures on the cantilevers to mitigatethe inherent stickiness of water and other fluids, thereby optimizingsignals received from any pathogens onboard.

“We have engineered the cantilever so that when we submerge it inwater, air is trapped on it; it effectively moves as if in air, so thedamping effect is minimized and the source becomes easier to detect,”he explains. The highly-sensitive cantilevers may ultimately be used todetect proteins, viruses, bacteria, DNA and other biomolecules.

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Associate Professor KAMIL EKINCI (ME, MSE)

“ ”We are designing diving-board-like cantileversto detect trace amounts of pathogens in a fluid.The textured surfaces of these specialcantilevers mitigate the inherent stickiness ofwater and other fluids, thus optimizing signalsreceived from any pathogens onboard.

NO SWIMMING ALLOWEDNanoscale Diving Boards that Detect Pathogens

A FIRST RESPONDER’S DREAMPortable, Noninvasive Imaging of Brain Injuries


Lecturer CALEB FARNY (ME)

“ ”We’re working to improve imagingtechniques of soft tissue in the brainthrough the skull using ultrasound.The goal is to develop a portabletranscranial imaging modality thatallows the skull layer to remain intact.

In collaboration with researchers at Brigham &Women’s Hospital, Lecturer Caleb Farny (ME) isdeveloping an unprecedented, ultrasound-basedimaging technology for the U.S. Army that coulddetect foreign objects that penetrate the skull, oridentify regions of blood pooling or hemorrhagingthat result. Ultrasound offers a low-cost, low-power, portable, radiation-free solution that’seasily deployable in the field, but getting it toperform as specified is no easy task.

“It’s difficult to image soft tissue through theskull, and high-frequency ultrasound doesn’t passwell through thick bone layers,” says Farny. “We’re

developing imaging methods that correct forsignal distortion coming from two differenttypes of sound wave propagation—longitudinaland shear mode—that the skull introduces.”

Longitudinal waves travel and oscillate in thesame direction, whereas shear mode wavesoscillate perpendicular to the direction of travel.Like noise-cancelling headphones, Farny’sultrasound device cancels out sound comingthrough the shear mode wave, yielding asharper image of soft tissue beneath the skull—and could add a new imaging modality beyondMRI and CT-scans.

Associate Professor James Galagan’s (BME) group and fourcollaborating research teams are building molecular maps of theregulatory and metabolic networks of the bacterium that causestuberculosis, all to determine which proteins and genes in thesenetworks trigger the disease. This knowledge could yield simpler,faster, more targeted diagnostics and drugs for TB, which causesabout two million deaths each year.

To map the bacterium’s regulatory network, the researchers applygenome sequencing technology to obtain a “circuit diagram” of thenetwork’s 180 known transcription factors, interconnected proteins

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Myobacterium tuberculosis bacteria. Associate Professor James Galagan (BME) is taking asystematic approach to pinpointing the genes and proteins in the TB bacterium that triggerthe disease. (Image courtesy of Centers for Disease Control and Prevention)

that activate or deactivatethe approximately 4,000genes controlling the cell.Applying a syntheticbiology technique, theynext activate thetranscription factors—individually and in groups,or “subcircuits”—to seewhich genes get turnedon or off as a result.Finally, they integrate thedata into a predictivecomputer model, whichthey use to pinpointpromising gene andprotein subcircuits toknock out.

“What’s unique aboutour approach to TB is thatwe’re trying to map outthe terrain in asystematic, unbiased andcomprehensive way,” says Galagan.

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Associate ProfessorJAMES GALAGAN (BME)

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We’re attempting to reverse-engineerregulatory and metabolic networks in thetuberculosis bacterium to determine whichproteins and genes trigger the disease. Bypinpointing these proteins and genes, wehope to pave the way for simpler, faster,more targeted diagnostics and drugs for TB.

DECONSTRUCTING TBHoning in on Potential Drug Targets

NIPPED IN THE BUDTargeted Chemotherapy for Lung Cancer Patients

Professor MARK GRINSTAFF(BME, MSE)

The leading cause of cancermortality in the U.S., lungcancer is remarkablydifficult to cure. Standardpractice for early stage lungcancer is to surgicallyremove, or resect, lungtissue tumors, but nearly 30percent of patients receivingsuch treatment developrecurrent disease, and only60 percent survive after fiveyears. Systematic injectionof paclitaxel, the standardchemotherapy agent forlung cancer, deliversinadequate concentrationsof the drug to diseased lungtissue and damages healthyorgans, but Professor MarkGrinstaff’s (BME, MSE)approach overcomes these drawbacks.

Upper panel shows scanningelectron micrographs of particlesbefore (left) and after (right)swelling; lower panel showsflexibility of a wet polymer film(scale bar: 5 mm). (Source:Annals of Surgical Oncology)

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We’re exploring the useof nanoparticles andflexible films for thedelivery of anticanceragents to treat lungcancer. The idea is totake advantage ofunique materialproperties offered bythese technologies toincrease the efficiencyof drug delivery.

Developed withcollaborator Dr. YolandaColson, a cardiothoracicsurgeon at Boston’s Brighamand Women’s Hospital,Grinstaff’s idea is to resect thetumor and apply paclitaxel viapolymeric nanoparticles orfilms at the margin duringsurgery. The nanoparticlesexpand and release the drugupon entering tumor cells; theflexible, conformal films canbe stapled directly to theresection margin and elute thedrug over several weeks.

Tests show that cancerousmice treated with thenanoparticles or filmsperformed significantly betterat killing tumors that thosereceiving conventionalchemotherapy treatment.

Brain disorders constitute a major unmet medical need; most arecurrently untreatable, and available treatments often involveserious side effects. But Assistant Professor Xue Han (BME) isconfronting this challenge head-on. She has developed noveltechnologies to control the brain’s neural network and identifyneurons within the network that go awry in neurological andpsychiatric disorders.

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Shown is a neuron in the brain genetically altered to express light-activated proteinchannelrhodopsin. This neuron can be precisely controlled with pulses of light.

“With technology we’vedeveloped to optically controlspecific brain cells using pulsesof light, we can simultaneouslymonitor and control neuronalactivity within the brain,” saysHan. “Our challenge is to usethis technology to establishcausal links between neuraldynamics and behavioralphenomena, from memory lossto abnormal movements.”

Han is currently using thetechnology to investigate theneural circuit principles ofneurological and psychiatricdiseases, with an ultimate goalof developing circuit-basedbiomarkers for brain disorders.

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Assistant Professor XUE HAN (BME)

“ ”Our research focuses on developing radical newgenetic, molecular, optical and electricalneurotechnologies to understand and treat braindisorders. Toward that end, we have pioneeredseveral technologies for optically controllingspecific brain cells using pulses of light.

MIND ALTERINGOptical Neurotechnologies to Probe and Correct Brain Disorders

CATCHING THE WAVEA Faster, Cheaper Way to Grow Tissue

Associate Professor GLYNN HOLT(ME)

In collaboration withresearchers from ClemsonUniversity and RiversideResearch Institute,Associate Professor GlynnHolt (ME) and AssociateProfessor CatherineKlapperich (BME, MSE)are advancing a novelacoustic method to form amicro-patterned scaffoldto grow artificial skin orother biological tissue. Themethod exploits Faradaywaves, which, in a thinliquid film, exhibit a varietyof patterns and patternspacings that can befrozen instantaneously.Through simpleadjustments in theacoustic method orscaffold material, the

Associate Professors Glynn Holt (ME) and Catherine Klapperich (BME, MSE) areadvancing a novel acoustic method that exploits Faraday waves (shown here inwater) to form a micro-patterned scaffold for use in the growth of artificial skin orother biological tissue.

“


”

Our research seeks tofreeze, on thenanosecond time scale,wave patterns createdby acoustics onsuitable polymermaterials. This wave-freezing technique canpotentially producemicro-patterned solidmaterials much morequickly andinexpensively thancurrent techniques, andcould be used as analternative method forengineering scaffoldstructures for tissuecell growth.

researchers can alter thesepatterns and spacings toachieve desired specifications.

Compared to traditionalmethods such asphotolithography, freezingFaraday waves offer a faster,cheaper, less complex andmore reliable way to producethe small pore size (100microns) that enable epithelialcells—which form the ultrathinsurface layer of the skin andother organs—to adhere totissue-engineering scaffolds.

By transmitting sound wavesat the right frequency, theresearchers are able to achievethe desired pore size. Using atransducer set at 30 kilohertz,they have reliably producedapproximately 100-micronpores across a large surface.

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Professor MARK HORENSTEIN(ECE)

All methods aimed atsystematically delivering drugsbeneath the skin either requireusing micro-needles or dosevery slowly, but ProfessorsMark Horenstein (ECE) andDavid Sherr (School of PublicHealth) are advancing anapproach that avoids thesedrawbacks and may ultimatelypermit the rapid inoculation oflarge populations.

To inoculate someonerapidly, one must direct avaccine into the stratumcorteum, the system of cellslying just under the outer skinlayer that has a direct pipelineto the immune system. With

Professors Mark Horenstein (ECE), left, and David Sherr (School of Public Health)examine a prototype of their nano-pulse patch, which would deliver drug-ladennanoparticles through the skin. Fluorescent dye helps track the movement ofnanoparticles through the body.

that goal in mind, theresearchers are working touse electrostatic force todrive drug-encapsulatednanoparticles about 10microns below the outerlayer of the skin, where thestratum corneum resides,and track their pathway tothe immune system.

Ultimately, they hope todevelop a portable fieldinstrument that can be usedin a doctor’s office or by anemergency medicaltechnician for the painlessand rapid inoculation of largepopulations in the event of abioterror attack.

“”

We are developing amethod for transdermal,needle-free drug deliveryin which drug-ladennanoparticles are forcedinto the skin using anelectrostatic pulse. Ifsuccessful, the techniquecould be used for therapid inoculation of masspopulations, or as apreferable alternative toordinary drug delivery.

NO NEEDLES, PLEASEAn Electrostatic Method for Pain-Free Inoculation

SHARPER IMAGEA Blur-Free Scanning Method for Improved Heart Monitoring


Professor W. CLEM KARL (ECE, SE)

The leading cause of mortality in industrializednations, coronary artery disease is characterizedby chronic inflammation and plaque formation inthe arterial walls, which, if not properly diagnosedand treated, can lead to a heart attack. Accuratedetection of the degree of inflammation couldhelp prevent heart attacks, but current diagnostictechniques, some quite invasive, fall short. Evenpositron emission tomography (PET), which cannoninvasively image arterial inflammation, iscompromised by severe blurring induced bycardiac and respiratory motion during lengthyPET acquisitions.

Now Professor W. Clem Karl (ECE, SE),graduate student Sonal Ambwani (ECE, PhD’11)

“”

We’re working to enable high-resolution, highsignal-to-noise imaging of coronary arteryinflammation through PET-CT scans. Thetechnology could be used to monitor plaquedevelopment in high-risk patients and tovalidate the effectiveness of potential drugsdesigned to reduce arterial inflammation.

and physicians from MassachusettsGeneral Hospital have joined forces todevelop an advanced technique thatcombines PET and CT scanning to eliminatethat blurring and, for the first time, providesnoninvasive, direct, sharp in vivo images ofdeveloping coronary plaques.

Combining image processing and motionestimation techniques to allow directvisualization of inflamed arteries, the newPET-CT coronary artery inflammationdetection method compensates for cardiacand respiratory motion and boosts imageresolution in computer simulations. Nextstep: clinical studies.

College of Engineering researchers have developed a new high-resolution PET reconstruction method that compensates for motionallowing direct non-invasive monitoring of coronary.

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TIPPING POINTSLung Cancer Biomarkers Present New Drug Targets

Much of the cellularmachinery behind biologicalprocesses unique to cancercells is run by a command andcontrol system called signaltransduction, which itself ispartly controlled by a processcalled phosphorylation. Whena protein is phosphorylated, iteither becomes active orrepressed, depending on itsspecial function. Identifyingthe phosphorylation status ofproteins in cancer cells versusnormal cells provides a uniqueability to understand andpossibly intervene with thecommand and control centerof cancer cells.

Professor Simon Kasif(BME), Assistant ProfessorMartin Steffen (BME, BostonUniversity School of Medicine)and their collaborators have

identified several proteinswhose activationsignature—which indicatestheir phosphorylationstatus—enables scientiststo distinguish between lungcancer and normal lungtissue cells with almost 97percent accuracy. They havealso developed a newcomputational strategy toanalyze this data andidentify specific sub-networks of biologicalpathways, or molecularcircuits, which are active incancer and dormant innormal cells.

The researchers’ findingsmay ultimately lead to thedevelopment of drugsdesigned to inhibit theseproteins, particularly in lungcancer patients.

Professor SIMON KASIF

(BME)

“”

We have identifiedproteins that distinguishlung cancer cells fromnormal lung tissue cells.Collections of theseproteins may serve astargets for future anti-cancer drugs.

POINT-OF-CARE:Infectious Disease Diagnostics on a Chip


Associate ProfessorCATHERINE KLAPPERICH (BME, MSE)

The robust, inexpensive, easy-to-manufacture microfluidic chips,cartridges and “instruments” that Associate Professor CatherineKlapperich (BME, MSE) is developing integrate sample preparation,amplification and detection using micron-sized, “micro solid phaseextraction columns” to grab and concentrate nucleic acids from a fewhundred microliters of blood or other bodily fluid. The instruments used torun these extractions require no electricity to power and will be built fromlocally available materials.

“The columns and

chips could ultimatelybe used to collect andstore nucleic acidsfrom samples ofblood, urine or otherbody fluids potentiallyinfected with bacteria,a flu virus or anotherpathogen. Thetechnology is alsocapable of isolatingbiomarkers necessaryto diagnose, stageand monitormalignant tumors. It’sespecially suitable foruse in resource-limited communitiesbecause the extractedgenetic material doesnot require expensiverefrigeration orelectricity and thedevices are portableand easy to use.

Associate Professor Catherine Klapperich (BME, MSE) and ME PhD student Jacob Trueb havedeveloped a compact, inexpensive, bicycle-pump-powered, disease diagnostic device thatextracts and analyzes DNA and viral particles obtained from blood samples.

”We’re developing robust, inexpensive, handheldplastic chips and devices that extract nucleic acidsfrom complex human samples—technologies thatcould enable rapid, point-of-care diagnostics forinfectious diseases and cancer without the needfor electricity or refrigeration. These minimallyinstrumented systems could be a major stepforward in facilitating molecular diagnostics indeveloping countries.

Affecting an estimated 20million Americans and 300million people worldwide,asthma remains an enigma. It iswell-known that when thesmooth muscle coating anasthmatic’s lung airways isexposed to an allergen, it “hyper-constricts” and makes breathingdifficult. But scientists lack acomplete understanding of theintegrated mechanismsunderlying this process.

To learn more about thesemechanisms at the individualairway level, Professor KennethR. Lutchen (BME) usesultrasound imaging to examinehow isolated airway wallstructures and simulatedbreathing forces modulate theability of the airway smoothmuscle to create sufficient forceto hyper-constrict the airway. Hethen uses PET andHyperpolarized MRI imaging toinvestigate how a real lung,comprised of hundreds ofairways in a complex branchingstructure, constricts in asthmaticversus healthy subjects.

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Three-dimensional computer rendering of the human airway tree. Colors representdistinct lobes.

“By matching images of airways with a three-dimensionalcomputer model of the lung, we determined that the smallest ofairways contribute the most to constriction, and the worseconstrictions tend to occur in localized clusters,” Lutchen says.“Our next step is to use these findings to establish how asthmaat the single-airway level leads to emergent clusters of verypoorly ventilated clusters of airways during an attack.”

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Professor KENNETH R. LUTCHEN (BME)

Dean, College of Engineering

“”

We are trying to understand how different structuresthroughout the airways change so that individualairways are capable of asthmatic hyper-constriction,and further which airways throughout the branchingairway tree constrict most during an asthmaticattack. Through this understanding, we hope toidentify potential therapeutic drug targets.

TREE WORKProbing the Lung’s Branching Airways to Improve Asthma Treatment

GETTING THE RIGHT DOSEEngineering More Effective Drugs for Lung Disease

Research ProfessorMALAY MAZUMDER(ECE)

Designed to administer drugsto the lungs in the form of drypowder particles, dry powderinhalers require patients toinhale deeply, hold theirbreath and exhale at aprescribed rate. As a result,many respiratory diseasepatients—from very youngchildren suffering fromasthma or cystic fibrosis, tooctogenarians withemphysema—end up withinsufficient doses ofmedication.

In collaboration withProfessor Mark Horenstein(ECE) and researchers at theBU Biomedical EngineeringDepartment, Boston MedicalCenter and Harvard School of

Laser-based instrument used to analyze the therapeutic aerosol produced by drypowder inhalers

“


”

Dry powder inhalersadminister drugs totreat diseases fromasthma to lung cancer,but current inhalerssuffer from manyproblems such as non-uniform blending,dose-to-dose variabilityand inefficient deliveryof active ingredients.We are developing newmethods forformulating drugparticles with animproved deliverysystem to meet criticalclinical needs.

Public Health, ResearchProfessor Malay Mazumder(ECE) aims to overcome thisdrawback. “Our goal is todevelop a formulation so thatdespite a wide variation ininhalation flow rates, we canadminister the drugsuccessfully,” he says.

Toward that end, theresearchers are engineeringdrug particles with diametersof one to three micrometers—the ideal size to reach thelung—and lactose “carrier”particles that prevent the drugparticles from sticking together.They expect the newformulation will lead to easier,more effective drug delivery fora wide range of patients.

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Professor AMIT MELLER(BME, MSE)

When it comes to genetictesting, today’s DNAsequencing technology is notready for prime time. Becausethis technology typically relieson time-consuming, expensive,error-prone DNA replicationtools, sequencing a humangenome can take over one weekand cost well over $5,000.

But a new DNA sequencingmethod advanced by AssociateProfessor Amit Meller (BME,MSE) that exploits solid-statenanopores—tiny, nearlycylindrical, silicon nitridesensors that optically detectDNA molecules as they passthrough the pore—requires farfewer DNA molecules thanconventional technologies,achieves greater accuracy, andmay ultimately enable clinicians

Professor Amit Meller (BME, MSE) is advancing an ultra-fast, low-cost DNAsequencing method that uses electrically-based nanoscale sensors withoptical readout.

to sequence an individual’sentire genome for as little as$100 in a matter of hours.

Combining opticaldetection capability with theability to analyze extremelylong DNA molecules withsuperior sensitivity, theteam’s solid state nanoporesare uniquely positionedto compete with the mostadvanced DNA sequencingmethods for accuracy, costand speed. Meller iscollaborating withresearchers from theUniversity of MassachusettsMedical School inWorcester to refine hismethod, and foundedNobleGen Biosciences in2010 to commercialize thetechnology. “

”

We’re advancing rapid,accurate, inexpensivemethods foramplification-freedetection and sequencingof individual DNAmolecules. Our researchcould vastly improveclinicians’ capability todiagnose patients’susceptibility to certaindiseases and tolerance forselected drugs.

THE $100 GENOMEFaster, Better, Cheaper Personalized Medicine

LOOK INSIDELow-Cost, High-Res, Deep Imaging of Bodily Organs

A problem with using light toimage inside tissue is thattissue is basically opaque,either absorbing or scatteringmost of the incoming light. Toaddress this problem,Associate Professor JeromeMertz (BME) has devised anumber of strategies.

One technique he’sdeveloped called HiLomicroscopy “numericallyrejects” out-of-focus hazethat appears alongside what’sin focus in an image of tissue,resulting in a higher-contrastimage. Using a normal imageand one made noisy by usingstructured illumination, onecan infer what is out of focusin the normal image, and then

Frame from video of chick embryo vasculature acquired with a fiber bundleendomicroscope. Left: Raw image through fibers. Middle: Sampling-correctedimage. Right: HiLo image with out-of-focus background removed.


numerically subtract it out.Boston Medical Centergastroenterologist Satish K.Singh is now using a HiLo-enhanced endoscope toexamine fluorescently-labeledstructures in colon tissue insearch of signs of disease.

Mertz is also developingtwo label-free strategies tohelp clinicians pinpoint signsof pathology inside tissue.One uses light to locally heatabsorbing structures so theybecome easier to image; theother couples ultrasound withlight to enhance high-resolution imaging in thicktissue, with potentialapplications in imaging thecolon and other organs.

Associate Professor JEROME MERTZ (BME)

“”

We’re developingnew low-cost, high-resolution imagingtechniques using lightto image inside tissuein the brain, colonand other organs.

Most bone fractures heal by forming cartilage at thefracture site. The cartilage becomes mineralized,eventually transforming into new bone tissue. Untilbone forms at the facture site, however, fracturehealing cannot be monitored in vivo using standardimaging technology.

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The new CT scanning technique allows researchers to see where andhow much cartilage (shown in blue) has formed relative to the boneshaft (red). The new technique also identifies other soft tissue (yellow)that surrounds the bone fracture.

“If we could see cartilage with an X-rayor CT scan, we could see much earlierthan is currently possible whether or notthe healing process is on track,” saysAssociate Professor Elise Morgan (ME,MSE). As a result, clinicians could applyearly interventions when needed andbetter predict when a patient couldresume weight-bearing activities.

To enable early assessment of bonefracture healing, Morgan has developed aCT-scanning technique that uses acontrast agent developed by AssociateProfessor Mark Grinstaff (BME, MSE) tolabel cartilage at the fracture site. “Thetechnique provides a three-dimensional,time-evolving map of cartilage and bonethat offers much more real-time feedbackon treatment progress,” says Morgan,who is now testing the technique withresearchers in orthopedic surgery throughanimal studies at Boston UniversityMedical Center.

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Associate Professor ELISE MORGAN (ME, MSE)

“ ”We are developing a minimally invasivediagnostic technique to track theprogress of healing of bone fractures.The technique could help cliniciansidentify complications early and takemeasures to accelerate fracture repair.

ALL IN THE CARTILAGEImaging Diagnostics for Bone Fracture Healing

OF LASERS AND LEDSFighting Pathogens with UV Technology

Professor THEODORE MOUSTAKAS(ECE, MSE)

Professor TheodoreMoustakas (ECE, MSE) isdeveloping two UV lighttechnologies withapplications ranging frommilitary communication tobiodefense. Made fromaluminum gallium nitridealloys, they could collectivelyidentify and neutralizepotential pathogens.

The first, a handheld,electron-beam pumpedsemiconductor laser, isexpected to be the first tooperate within the deep UVregion of theelectromagneticspectrum. Because of itsultra-low emissionwavelength (below 250nanometers) and compactsize, such a laser couldprovide point-of-care

Professor Theodore Moustakas (ECE, MSE) inspecting the growth of nitride-basedsemiconductor materials.

“


”

We’re developinghandheld, deepultraviolet (UV)lasers that could beused to analyze apatient’s blood at thepoint of care, andUV-LEDs that couldimmobilize certainviruses, including theavian flu virus, andthus be used tosterilize medicalinstruments.

chemical analyses of blood orother bodily fluids. Incollaboration with AssociateProfessors Roberto Paiella andLuca Dal Negro (both ECE,MSE) and industrial partners,Moustakas is developing aprototype sized below onecubic inch.

The second, highly energy-efficient LEDs that emit lightin the UV-C range (200-290nanometers), may not onlydetect pathogens but alsodamage microorganisms’DNA—and therefore be usedfor surface decontaminationin hospitals. Nucleic acids inDNA and RNA absorb UVradiation within this range; aUV light source at 266 nmprevents an organism’s DNAand RNA from replicating,thereby killing it.

Professor KENNETH R. LUTCHEN (BME)

Dean, College of Engineering

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Professor IOANNIS PASCHALIDIS(ECE, SE)

Despite spending about $2trillion annually on healthcare,the U.S. recently ranked lowestamong 19 industrializedcountries in its rate of“preventable” deaths. Butmedical experts believe that amore proactive, data-drivenhealthcare managementstrategy could yield dramaticimprovements in healthoutcomes and significantlylower costs.

To that end, Professor IoannisPaschalidis (ECE, SE), DanielNewman, Boston MedicalCenter (BMC) Chief MedicalInformation Officer DanielNewman, and Shiby Thomas,BMC director of enterpriseanalytics, are pursuing acomprehensive and systematicapproach to intelligentlyprocessing electronic healthrecords (EHRs) and wireless “

”

We’re applying datamining and optimizationtechniques to electronichealth records andwearable sensor data toproduce algorithms thatassess patients’ healthrisks and predict futurehealthcare needs. Theautomated, dynamicsystem that we’redeveloping could enablemore effectivepreventative care andreduce overallhealthcare costs.

DATA-DRIVENAlgorithms for Better, Cheaper Healthcare

body sensor data, anddirecting physician attentionto preventing serious medical conditions.

Paschalidis plans to applydata mining and optimizationtechniques to electronic,clinical practice data from theBoston Medical Center,associated insurance claimsand information fromwireless, wearable sensors toproduce algorithms thatplace patients in differentrisk-based clusters(reclassifying them whenindicated by new data),provide a predictive modeland physician-recommendedactions specific to eachcluster, and indicate optimumhealthcare managementapproaches for specificchronic conditions likediabetes and heart disease.

SOUNDING OUT TUMORSCombining Nanomedicine and Ultrasound for Targeted Cancer Therapy

Assistant Professor TYRONE PORTER(ME)

Treatment options for solid,cancerous tumors includesurgery, which is invasive andoften requires a lengthyrecovery, and chemotherapy,which is damaging to healthytissue, can compromise theimmune system and produceother debilitating side effects.Assistant Professor TyronePorter (ME) has developedtwo far less toxic techniquesthat combine nanotechnologyand focused ultrasound to killlocalized malignancies rapidlywithout damagingsurrounding cells and tissues.

Developed with BostonUniversity School of Medicineoncologist David C. Seldin,the first technique usespressure-sensitive liquidnanodroplets loaded withcancer therapeutics. Smallenough to leak through tinyopenings in blood vessels

Nanodroplets for delivery of therapeutic agents—a research collaborationbetween Assistant Professor Tyrone Porter (ME) and BU School ofMedicine Professor David Seldin. (Image by of Aysegul Yonet)

“


”My group combinesnanotechnology andultrasound to targetsolid tumors moreprecisely, boththrough novel drugdelivery and thermalablation techniques.

within solid tumors andaccumulate in the interstitialspace between cancer cells, thenanodroplets are vaporizedwith focused ultrasound,releasing their payload at thetumor site.

Porter’s second technique,developed in collaboration withNathan McDannold, researchdirector of the Brigham andWomen’s Hospital/ HarvardMedical School FocusedUltrasound Laboratory, is toproduce liquid perfluorocarbonnanodroplets that accumulatewithin solid tumors after beinginjected into the bloodstream.Upon reaching the tumor site,the nanodroplets are vaporizednoninvasively with high-intensity focused ultrasoundpulses, yielding bubbles thatincrease ultrasound absorption,producing sufficient heat to killthe cancer.

High-intensity focused ultrasound (HIFU) can projectacoustical energy into tissue and generate localized heatingat depth—literally “cooking” the region of exposed tissue. Akey challenge in HIFU therapy is to accurately heat targetedtissue volume with minimal damage to surrounding tissue.

A solution devised by Professor Ronald Roy (ME) useslaser irradiated nanoparticles to promote small amounts of

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Laser-irradiated nanoparticles can nucleate cavitation activity in thepresence of high-intensity focused ultrasound, resulting in a substantialenhancement of acoustic emissions levels.

acoustic cavitation, which helpsconvert acoustical energy into heat.A single flash of laser light heats theparticles, forming nanoscale vaporcavities that evolve into a cavitationbubble field when exposed to HIFU.The heated nanoparticles promotecontrolled cavitation productionwith greater precision and lessultrasonic energy. Laser irradiatednanoparticles can also be used inconjunction with short-pulseultrasound to achieve photo-acoustic imaging at depth.

“The advantage of cavitation isnot to generate bulk heating, but anacoustic emission—which occurswhen the bubble collapses,” saysRoy. “We’ve shown that goldnanoparticles increase the acousticemission response 100-fold overconventional photoacoustics,enabling much deeper imaging.”

Roy envisions an apparatus thatswitches from imaging (shortacoustic pulses) to therapy (longpulses) mode at the turn of a dial.

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Professor RONALD A. ROY (ME)

“”

We combine nanoparticles with laser light andfocused ultrasound to image tissue structuresand/or thermally lesion tumors and otherdiseased tissue more precisely and reliably. Thesenanoparticles can be designed to adhere tospecific tissue types, such as tumor cells, enablingtissue-specific targeted imaging and therapy.

AT THE TURN OF A DIALNanoparticle-Assisted Ultrasound for Tumor Imaging and Therapy

GOING WITH THE FLOWSound Wave-Driven, Microfluidic Biochips for Cancer Drug Discovery


Assistant ProfessorMATTHIAS SCHNEIDER (ME)

Today’s cancer drugs target notonly cancerous cells, but alsomany other fast-growing cellsthroughout the body, leading toweakened immune systems andother side effects in patientsundergoing radiation andchemotherapy. But a newthumbnail-sized, acoustics-driven, microfluidic biochipdeveloped by Assistant ProfessorMatthias Schneider (ME) andcollaborators in Austria andGermany could help uncover newstrategies for identifying moreeffective therapies.

Using surface acoustic waves(SAW) with amplitudes spanninga few molecules, the researcherspump minute amounts of liquidcontaining protein-coated micro-and nanoparticles toward cancercells on the chip’s surface. Similarto pumping blood througharteries, the waves creates a flowin which the particles, designedto adhere exclusively to thecancer cells, are dispersedtoward their targets.

““These biochips will allow us to critically and objectively

evaluate the efficiency of micro- and nanoparticle-based drugdelivery vehicles,” says Schneider. “This is crucial, sinceidentifying ineffective strategies is sometimes more importantthan finding new ones.”

Microfluidic SAW chips could be used in high-throughput experiments to criticallyevaluate old and new approaches to treating cancer and other diseases. (Source:Lab on a Chip)

”Using the principles of sound, wecreate nano-earthquakes to mimicblood flow along the surface ofmicrofluidic biochips. These chips areused in fundamental and appliedresearch to advance novel approachesto treating cancer and other diseases.

When a future pandemic breaksout, public health officials mayhave a high-production vaccinefactory at their disposal, thanksto researchers at the FraunhoferUSA Center for ManufacturingInnovation at Boston University.Working with the FraunhoferUSA Center for MolecularBiology in Delaware and thebiopharmaceutical company iBio,Inc., they’ve developed a fullyautomated “factory” that usestobacco plants to produce largequantities of biological medicineswithin weeks.

This first-ever, plant-basedvaccine factory exploits thetobacco plant’s well-understood,genetically engineeredmechanisms for producingspecific proteins within theleaves and stalks. The factoryconsists of a series of roboticallytended machines that plantseeds, nurture growing plants,insert genetic instructions onwhat to produce, and harvestplants at maturity.

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Plant-based vaccine factory, developed by Fraunhofer/BU College of Engineering,consists of robotically tended machines that plant seeds, nurture growing plants,insert genetic instructions on what to produce and harvest plants at maturity. (Imagecourtesy of Fraunhofer USA Center for Manufacturing Innovation at Boston University)

“Even though the process of making vaccines from plants isalmost like farming, we treat it like an automatedmanufacturing process,” says Professor Andre Sharon (ME),director of the Fraunhofer Center at BU. “That’s how we cancost effectively scale it up from a few milligrams in laboratorydemonstrations to many kilograms in case of a pandemic.”

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Professor ANDRE SHARON (ME)

“ ”We have developed a tobacco plant-based vaccine factory that could beused for high-volume vaccineproduction to address pandemics andother time-critical public health needs.

VACCINES ON-DEMANDHigh-Production Factory Extracts Medicines from Tobacco Plants

In a recent study published in PNAS, Professor Barbara Shinn-Cunningham (BME) and hercoauthors explored why some people with normal hearing have difficulty understandingconversations in complex auditory environments such as bars.


CAN YOU REPEAT THAT?Advancing Better Hearing Diagnostics and Aids

Professor BARBARA SHINN-CUNNINGHAM (BME)

Overexposure to loudmusic is known to causepermanent hearing loss,but new researchsuggests that even beforea typical audiologicalexam can detect thedamage, such exposuremay interfere witheveryday communication.An individual may have“normal hearing” basedon standard tests thatmeasure the quietestsound a person can hear,yet still have troubleunderstanding what herbest friend is telling her ata crowded bar.

A study led byProfessor Barbara Shinn-Cunningham (BME)indicates that the problemmay lie in the “first-responder” portion of theauditory system, whichencodes the detailedstructure of incomingsounds before the brainprocesses them further.

“ ”Our research introduces more precisemeasures of auditory processingimpairments than are in use in today’saudiologists’ offices—measures thatcould lead to improved hearingdiagnostics and hearing aid technology.

Until now, scientists didn’t know if this problem was due toimpairments in the cortex, where decision-making and languageprocessing occur, or earlier in the auditory system, where basicsensory information is first encoded. “Our results suggest that thefidelity of early sensory encoding in the subcortical brain determinesthe ability to communicate in challenging settings,” Shinn-Cunningham explains.

The study’s findings could lead to more effective hearingdiagnostics and hearing aids.

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SHAPE MATTERSA New Pathway to Anti-Cancer Drugs and Tissue Engineering

Assistant Professor MICHAEL SMITH

(BME)

To interrogate its surroundings,a cell relies on two-nanometer-wide receptors onits surface. These receptors areconfigured to bind to a fibrousprotein matrix in the localmicroenvironment, butexternal forces can stretch thisfiber, adversely impacting thereceptors’ ability to latch ontoit. As a result, the cell maymiss out on vital information,such as instructions to cancercells to stop proliferating.

To better understand themechanisms behind thisprocess, Assistant ProfessorMichael Smith (BME) isprobing “nonequilibriumbinding sites”—thoseperturbed by force—with aspectroscopic device called

FRET and an atomic forcemicroscope (AFM). FRET isa nanoscale ruler that candetermine if a protein hasbeen stretched; the AFM isused to image the cell’ssurroundings at nanometerresolution and detectbinding sites that getexposed when the proteingets stretched.

By uncovering non-equilibrium proteinconformations in the localcellular environment andtheir impact on cellsignaling, Smith aims toidentify new drug targetsand approaches to stemcell-based therapeutics forregenerative medicine andtissue engineering. “

”

I’m interested in howforces change the shape,or conformation, ofproteins that cells use tointerrogate theirsurroundings—fibrousproteins that mayultimately bemanipulated to growdesired stem cells or haltthe spread of cancer. Mymain goal is to useadvanced tools toinvestigate the impact offorces on these proteinsat the nanoscale level.

The image illustrates how microfabricated surfaces and a spectroscopic toolcan be used to understand protein behavior in a 1 micrometer diameterextracellular matrix fiber of fibronectin. Fiber stretching with the tip of a MEMSdevice is accommodated by unfolding of fibronectin molecules into non-equilibrium protein conformations. After release from the tip, the fiber relaxesback to its initial length through a process that involves molecular refolding intoits equilibrium state. The green color in the fiber results from a nanometer scalespectroscopic label on the fibronectin molecules that provides informationabout the molecular conformation within the fiber.

BREATHING FREENew and Improved Mechanical Ventilators

Professor BELA SUKI (BME)

A potentially life threateninglung condition leading to lowblood oxygen levels, acuterespiratory distress syndrome(ARDS) requires admissionto an intensive care unit andmechanical ventilation. But ofthe approximately 100,000ARDS patients admitted toICUs each year, only about60 percent survive.

One reason is that thevolume of air thatconventional ventilatorsperiodically deliver to thelung is fixed. “People don’tbreathe that way,” saysProfessor Bela Suki (BME). “Abiologically variableventilator that mimics naturalbreathing and is optimizedfor presenting conditions—from pneumonia to organ

Ventilator modified by Suki’s group to deliver variable ventilation.

“


”

We are developing atechnology toventilate people inthe ICU in an optimalmanner so that theyrecover from acutelung injury faster. Thetechnique has beentested in small andlarge animals, and itworks very efficiently.

failure—would provide betteroxygenation and lungfunction.”

In the past 10 years, Suki’sresearch group determinedthat variable ventilationimproves oxygenation andstimulates lung cells tosecrete surfactant, a lipid-protein mixture that’s criticalfor breathing. In collaborationwith Boston (University)Medical Center pulmonarymedicine specialist GeorgeO’Connor, Suki has modifiedexisting human ventilators todeliver variable ventilation,conducted hundreds of animaltests in his laboratory andpatented the technology. Thenext step is to obtain FDAapproval and start a smallclinical trial.

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Associate Professor JOE TIEN(BME)

One of the biggest problems intissue engineering is thevascularization of engineeredtissue. While skin grafts for aburn victim can wait longenough for blood vessels togrow into them, largerstructures such as muscle andheart tissue need immediateaccess to blood vessels orthey will die from lack ofoxygen and nutrients.

To avoid this problem,Associate Professor Joe Tien(BME) is developing materialswith engineered blood vesselsalready inside. Starting with agel or polymer, he applieslithographic patterningmethods from the integrated

Image of a collagen-based biomaterial that contains internal channels to guide theflow of blood. The pairs of “ports” shown at the top and bottom could, in principle,be surgically connected to the vascular system of a recipient in which thebiomaterial is implanted.

circuit industry to carve outmicrofluidic networks in thematerials that mimic theshape and size of real blood vessels.

Among other things, thetechnology could be a boonto blast victims in militarytheaters worldwide.“Reconstructive surgery isquite advanced, but usually asurgeon takes tissue fromone part of the body andtransfers it to the other,” saysTien. “In severe cases, youneed to replace a largevolume of muscle or othertissue, and that’s where thebiomaterials we’redeveloping could help.”

“”

We build biomaterialsthat contain internalchannels that resemblethe human vascular(blood vessel) systemin scale and shape. Ourobjective is to providereconstructive surgeonswith new tools forforming complex three-dimensional tissuesthat require immediateperfusion with blood.

LIFELINES, LITERALLYEngineered Blood Vessels for Reconstructive Surgery

LABEL-FREEOn-Chip Pathogen Detection with Interferometry


ProfessorSELIM ÜNLÜ (ECE, MSE)

Rapid, chip-scale,low-cost detection ofviruses and otherpathogens is key tocontaining outbreaks,but today’s biosensortechnologies, whichtypically rely onfluorescent labels, areexpensive andcumbersome. Label-free biosensingdevices avoid thesedrawbacks throughadvanced photonicstechnology, but oftenlack sufficientsensitivity to detectnanoscale viralparticles.

Now a new, highlysensitive nanoparticledetection techniqueand device calledInterferometricReflectance ImagingSensor (IRIS)developed byProfessor Selim Ünlü’s(ECE, MSE) research

“group in collaboration with Professor Bennett Goldberg (ECE, MSE) andBoston University School of Medicine microbiologist John Connor,promises to pinpoint single virus and other pathogen particles with greaterspeed, accuracy and affordability than existing label-free techniques.

To detect and size up to a million potential pathogens in parallel, IRISshines light from multi-color LED sources sequentially on nanoparticlesbound to the vast sensor surface, which consists of a silicon dioxide layeratop a silicon substrate. Light reflected from the sensor surface is modifiedby the presence of particles, producing a distinct signal revealing the size ofeach particle.

Conceptual representation of H1N1 viruses (blue) captured by antibodies (orange) on the IRISsurface. (Image courtesy of Aysegul Yonet)

”We are developing a nanoparticle detectiontechnique/device with high sensitivity andspecificity that provides rapid, chip-scale,low-cost detection of viruses and otherpathogens. The technology could be usedin infectious disease diagnostics anddetection of potential bioterror agents.

An interdisciplinary team of College ofEngineering faculty members—ProfessorSandor Vajda (BME, SE), Research AssistantProfessor Dima Kozakov (BME), ProfessorIoannis Paschalidis (ECE, SE) and AssociateProfessor Pirooz Vakili (ME, SE)—aredeveloping powerful optimization algorithmsfor predicting the structures of complexes thatform when two cell proteins bond together—structures that, in some cases, generateerroneous cell signaling pathways that cantrigger cancer and inflammatory diseases.

“Protein-protein interactions represent anincreasingly important class of targets for thedevelopment of drugs,” says Vajda.“Understanding the atomic details of thecomplex frequently provides a good startingpoint for finding small molecules capable ofmodulating biological function. Anotherimportant application is to biotechnology,where the accurate prediction of interactionsbetween biologics such as engineeredantibodies and their cellular receptors offersthe basis for rational design.”

Many biologically important protein-protein interactions produce fragile complexesthat do not remain intact long enough topermit direct experimental analysis, butoptimization algorithms such as thosedeveloped by the College of Engineering team

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An interdisciplinary College of Engineering team has developedcomputational methods to predict the structures that form whentwo cellular proteins interact.

can determine the structure of these complexeswith great accuracy based on the structures of thecomponent proteins.

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Professor SANDOR VAJDA (BME, SE)

“”

We have developed algorithms to predict thestructure of complexes formed by protein-protein interactions involved in metaboliccontrol, signal transduction, gene regulationand other critical processes. These algorithmscould uncover new targets for drugs thatcombat cancer and inflammatory diseases.

MISSED SIGNALSFinding New Cancer Drug Targets Where Proteins Combine

HIGH CONTRASTNanoparticle-Enhanced Imaging for Heart Disease Detection

Associate Professor JOYCE WONG(BME, MSE)

Vulnerable plaques areunstable structures in anarterial wall that couldrupture in minutes to hours,leading to stroke, heartattack or pulmonaryembolism. AssociateProfessor Joyce Wong’s(BME, MSE) goal is todevelop magnetic resonancecontrast agents—using 20-nanometer-diameter ironoxide nanoparticles—todetect vulnerable plaquesbefore they rupture. Aided bythese nanoparticles, aphysician could determinewhether a plaque is likely torupture and needsimmediate treatment.

One of Wong’scollaborators, JamesHamilton, professor ofphysiology and biophysics at

By adding a marker to iron oxide particles, Wong aims to develop a noninvasivemethod for differentiating between stable and unstable arterial plaques in MRIs.

“


”We are developingiron oxidenanoparticles asimaging contrastagents to facilitatethe early detectionof heart disease.

the Boston University Schoolof Medicine and an affiliatedfaculty member in theBiomedical EngineeringDepartment, developed aunique animal model for thestudy of triggered plaquerupture—a model thatclosely resembles theprogression of disease inhumans. By injecting image-enhancing nanoparticles intothe arteries in these regions,physicians could examineplaques and determinepotential rupture sites.

“Based on our research,we envision a noninvasive,diagnostic kit that a doctorcould use to determine if apatient needs treatment forvulnerable plaques andsubsequently monitor thattreatment,” says Wong.

For Assistant Professor Muhammad Zaman (BME), the effectiveness of amedical device depends not only on the technology but also itsimplementation. “Engineers need to be aware of who is going to use thetechnology they design and where it is going to be used,” he says. “A lot oftechnologies fail because they’re brilliant ideas but not context-specific.”

Informed by that perspective, Zaman and students in his Lab forEngineering Education & Development are advancing several field-deployable medical technologies for resource-limited countries. Theyinclude a portable, microfluidic system that uses fluorescence-based

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Design of a microfluidic system for counterfeit detection in the field.

sensors to detectcounterfeit andsubstandardprescription drugs; a$20 cell phone-powered pulseoximeter that canmeasure bloodoxygenation andscreen for early signsof acute respiratoryinfection; and a simpletechnique that usesselected gels and otherinexpensive materialsto extend the shelf lifeof proteins, antibodiesand other biologicalcomponents neededfor HIV and othermedical tests.

“These devices areaffordable, durable andeasy to use, andaddress the particularneeds of specificcountries fromPakistan to Zambia,”says Zaman.

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Assistant Professor MUHAMMAD ZAMAN (BME)

“”

We are creating computational and experimental toolsto improve the quality of life and the practice ofmedicine in resource-limited countries. In this regard,we are working closely with the Center for GlobalHealth and Development and various medical schoolsand engineering institutions around the globe todevelop cheap, robust and easy-to-use solutions forimproved diagnostics and health data analysis.

SIMPLE, CHEAP AND DURABLEMedical Technologies for Resource-Limited Countries

BREAKING DOWN THE WALLSBiomechanical Model to Probe Cardiovascular Disease Mechanisms

and Potential Therapies


Assistant Professor KATHERINE YANHANG ZHANG (ME, MSE)

The leading cause of death in industrializedcountries, cardiovascular diseases (CVDs)account for 40 percent of all U.S. deaths,more than all forms of cancer combined.Many CVDs involve arteriosclerosis, orhardening of the arteries due to structuralchanges in blood vessel walls. To betterunderstand the underlying physics of arterialstiffness associated with CVDs, AssistantProfessor Katherine Yanhang Zhang (ME,MSE) aims to pinpoint the mechanisms thatcontrol structural and functional changes inblood vessel walls.

Toward that end, she is developing abiomechanical model of the vascularextracellular matrix, specialized proteinsthat provide structural support toblood vessels and the developmentof cells. Coupling molecular-levelstructural protein mechanicsto tissue-level behavior,this multi-scale modelcould enableresearchers andclinicians to probebasic mechanismsbehind CVDs and other

“ ”We’re developing and validating abiomechanical model of the vascularextracellular matrix, in order to probebasic mechanisms behind cardiovasculardiseases and other vascular diseases,and design new therapies.

vascular diseases, and eventuallydesign new therapies.

Ultimately, Zhang seeks to enablepatient-specific clinical studiescombining the multi-scale model andthree-dimensional vascular anatomyimaging capabilities. “This should beuseful in following diseaseprogression, especially regarding theinitiation and effects of arterialremodeling in CVDs,” she explains.

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Scanning electron micrograph images of arrays of microparticles of double-disk geometry (left) and nanoparticles of cylindricalgeometry (right). These precisely engineered magnetic particles can serve as MRI contrast agents.

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COLOR-CODEDPrecisely Engineered Magnetic Resonance Imaging (MRI)

Contrast Agents Using a Top-Down Approach

Professor XIN ZHANG (ME, MSE)

Using a top-down, engineering approachto the fabrication of nano- andmicroparticles yields precise control ofcritical features such as size and shape.Recently, this approach has been appliedto optimizing drug delivery as well asdeveloping novel MRI contrast agents.Now a research team led by ProfessorsXin Zhang (ME, MSE) and StephanAnderson, a radiologist at BostonUniversity Medical Center, is furtherdeveloping these approaches in thedesign of unique MRI contrast agentsusing biocompatible materials.

In collaboration with Anderson, Zhang and twostudents—graduate student Xiaoning “Travis” Wangand post-doctoral student Congshun Wang—havedeveloped fabrication techniques using photo- andelectron beam lithography employing biocompatibleiron oxides to yield precisely engineered, magneticnano- and microparticles. The precision engineeringaffords unique, tunable MRI “signatures” based onparticle size and shape as well as the particular ironoxide used in fabrication.

The tunability of these MRI signatures offers thepossibility of distinguishing various contrast particlessimultaneously using MRI, and color-coding particularcells or tissues of interest.

“”

We’re developing next generation, fabricatedcontrast agents for magnetic resonance imaging(MRI) which offer the potential of labeling anddifferentiating particular cells or tissuessimultaneously using MRI. This capability couldenhance cancer detection and characterizationand improve monitoring of cell-based therapies.

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RESEARCH CENTERS AND EDUCATIONAL PROGRAMSHealthcare technology is a major focus of several College of Engineering and BostonUniversity-wide research organizations and College of Engineering educational programs.

Research Centers and Initiatives> Biomolecular Engineering Research Center bmerc-www.bu.edu> Boston (University) Medical Center bmc.org> Boston University Photonics Center bu.edu/photonics> Center for BioDynamics cbd.bu.edu> Center for Biophotonic Sensors and Systems bu.edu/cbss> Center for Global Health & Development/Global Health Initiative bu.edu/cghd> Center for Information and Systems Engineering bu.edu/systems> Center for Memory and Brain bu.edu/cmb> Center for Nanoscience & Nanobiotechnology nanoscience.bu.edu> Center for Neuroscience bu.edu/neuro/research/cfn> Computational Genomics Laboratory bu.edu/bme/research/labs/cg

> Hearing Research Center bu.edu/hrc> Nanomedicine Initiative nanoscience.bu.edu/nanomedicine> Neuromuscular Research Center bu.edu/nmrc> NSF Smart Lighting Engineering Research Center at BU bu.edu/smartlighting> Wallace H. Coulter Translational Research Partnership bu.edu/bme/research/coulter/

Student Training and Research Programs

> Global Health Initiative bu.edu/eng/links/ghi

> CIMIT Healthcare Technology Prize cimit.org

> Cross-disciplinary Training Program in Nanomedicine for Cancer (XTNC) nano-cancer.bu.edu

> Engineers Without Borders http://blogs.bu.edu/ewbexec

> GAANN Fellowship bu.edu/eng/links/gaann

> Laboratory for Engineering Education & Development bu.edu/leed

> Translational Research in Biotechnology Program bu.edu/eng/links/trbp

Saving Lives, Cutting Costs BU College of Engineering

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Nanodroplets for delivery of therapeutic agents—a research collaboration between College of Engineering Assistant Professor Tyrone Porter (ME) andSchool of Medicine Professor David Seldin. (Image by Aysegul Yonet)

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