Discover article - Wyss Institute at Harvard

Wyss bioengineer Kit Parker (left, with Harvard graduate student Borna Dabiri) is studying howpressure waves from explosive blasts affect brain tissue.James Niemi, lead senior staff engineer at theWyss Institute, demonstrates James Collins’sConcussion in Miniaturevibrating shoe insoles, which help people withbalance and walking problems.Bioengineer Kit Parker, a major in the U.S. Army, was on duty in Afghanistan in 2009 when anexplosive struck the lead vehicle in his convoy. The driver and vehicle commander sufferedmajor concussions in the crash. Their behavior suggested the soldiers had suffered traumatic top, Ingber picks up a pair of oversize shoebrain injuries, or TBIs, which can have devastating long-term effects, including cognitive and insoles wired to small battery packs. HeThe psychiatric Wyss Institute’s disorders, suite seizures, of machining and early-onset tools Alzheimer’s disease. “I thought to myself,explains that elderly people often sufferincludes ‘There’s 3-D no printers first aid (one for this,’ of which ” Parker is shown says. at If the men had suffered a broken limb, he could havefar right) that make three-dimensional objectsfrom poor balance when the nerves in theirtied a splint, but he knew there was no way to immediately stop the cascade of damagingbased on computer-generated drawings. This Cancer-Fighting Factory feet lose sensitivity. The insoles producechemical events happening those soldiers’ brains. So he went back to his lab to find onewide himself. view is a composite of seven photos.vibrations that override those effects.Bioengineer David Mooney has packed cancer-fighting factory into what looks like a tablet ofThe solution Parker hit upon is a “brain on a chip,” a model of the traumatized brain that is a The key to making them work was notaspirin. With this new technology, he aims to improve treatment of melanoma, a deadly skindecades first step since, toward his understanding work has proven the effects of TBIs and how to halt them. To replicate the braincancer that can claim up to 85 percent of patientssearchingdiagnosedforafteranmetastasis.ideal vibrationTo start,frequency,otherwise.in miniature,He hasParkerdemonstrated,and his team startedforwith an elastic substrate about the size of a fingernail,Mooney’s team members biopsied a mouse tumor, but isolated recognizing some of how its proteins, complex and systems loaded inthen added a layer of cells on top to mimic networks of blood vessels in the brain. To replicateexample, that exerting a mechanical force them into the tablet, a biodegradable plastic device nature—like so porous that weather, it is 90 for percent example—respondair. Theythe traumatic effects on vascular tissue fromon a cell can activate cell signaling.also filled the tablet with GMC-SF (granulocyte macrophage colony-stimulating factor), anan improvised explosive device, Parker andto random signals in the environment.inflammatory protein known to attract immune cells.At his the team first used committee a high-speed meeting motor to in stretch Cambridge,the elastic Massachusetts, substrate by Ingber one-fifth found of an himself inchBiomedical engineer James Collins, whoThen they implanted the tablet under the mouse’s skin. As expected, GMC-SF triggered ared alert, attracting immune cells that flooded theinventedtiny device.theOnceinsoles,inside,knewthesethatimmunethe actcellssurroundedin just a fewbymicroseconds,other scientiststhenbreakingreleasecame in contact with the tumor proteins and learned of walking to recognize is itself them a as complex well. Before system—a too long,it. When they analyzed the samples of theboundaries—physicists publishingcontents of the tablet, including the trained immune dynamic cells, were interplay trafficked of the to the ground, lymph the nodes, walker’ssubstrate about 90 minutes later, theyin biology journals, biologists in physicsbiological garrisons that help the body recognize and fight germs. Once ensconced inside,found no evidence of increased cell deathfootwear, the countless nerves that enervatethe trained immune cells taught naïve counterparts to recognize the tumor and attack. “We’republications. or even simple The tearing. group But resolved they did to find form athe feet, and the brain that governs theable to shuttle millions of cells through this device, generating a very potent immune responseresearch that the center stretched that cells not were only hypersensitivetolerated but against the cancer cells,” Mooney says.process. Suspecting that a person’s gait couldalsotoencourageda protein thatthepromotessame kindconstrictionof interdisciplinarysensibility, and whose ideas would be to a complete regression in 40 percent of mice the weather, Collins tried delivering randomofIn 2009, Mooney reported that the device led be just as responsive to random signals asblood vessels. To Parker, the results suggestthat head trauma kick-starts a chemicalinspired by the now-burgeoning knowledge with metastatic melanoma. Yet the projectchain of events leading to a narrowing andpulses to elderly subjects’ feet. Sure enough,might have stalled if not for the Wyss, whereabout reshaping how nature of blood builds. vessels in the brain.the signals worked. The sensitivity of theMooney has been working with collaboratorsto develop efficient and low-costSwiss-born Over time, Parker billionaire speculates, Hansjörg the effect Wyss,nerves in the subjects’ feet was so thoroughlya HarvardcontributesBusinessto longer-termSchoolconsequencesgraduate, liked manufacturing techniques and to prepare restored that they were able to walk with thesuch as depression and a wide variety ofthe idea so much that he donated the single the cancer-fighting factory for human balance of a typical 20-year-old.neurodegenerative diseases.largest gift in Harvard history, $125 million, trials. The first tests, in fewer than aParker hopes to eventually use theYet the shoe inserts almost didn’t happen.dozen patients, will take place at theto make “brain it on happen. a chip” to The test school drugs tapped that can Ingber haltCollins developed the basic technology overDana-Farber Cancer Institute this year.to run the process. the show. If a compound administereda decade ago and started a company toimmediately after the simulated explosionwere to stop the cascade of chemicalFilled with tumor-specific proteins and turn his prototype into an actual product.In Parker’s “brain on a chip” (top), brain cellsSole events, Searchingthen it could be used at the site ofimplanted under the skin, the porous plastic But by 2009, a foundering economy had leftcultured on silicone form neural networksIngber an injury, and I just stop as inside a soldier a gleaming, would tie a splintdisk David Mooney developed reprograms the(bottom). Rapidly stretching the cells at highthe project in the fledgling prototype stage.500-square-foot on a broken limb. laboratory space with airy,body’s immune system to attack tumors.speed mimics mechanical blast forces.That might have been the end of it—onehigh ceilings. Standing at a black counter-more idea in the boneyard of promisingTHIS PAGE, CLOCKWISE FROM TOP: JON CHASE/HARVARD; SAM OGDEN; MATTHEW HEMPHILL/HARVARD SCHOOL OF ENGINEERING AND APPLIED SCIENCES. OPPOSITE: WYSS INSTITUTE; PHOTO RESEARCHERS/SCIENCE SOURCEDISCOVER3504.2013

Wyss bioengineer Kit Parker (left, with Harvard graduate student Borna Dabiri) is studying howpressure waves from explosive blasts affect brain tissue.James Niemi, lead senior staff engineer at theWyss Institute, demonstrates James Collins’sConcussion in Miniaturevibrating shoe insoles, which help people withbalance and walking problems.Bioengineer Kit Parker, a major in the U.S. Army, was on duty in Afghanistan in 2009 when anexplosive struck the lead vehicle in his convoy. The driver and vehicle commander sufferedmajor concussions in the crash. Their behavior suggested the soldiers had suffered traumatic top, Ingber picks up a pair of oversize shoebrain injuries, or TBIs, which can have devastating long-term effects, including cognitive and insoles wired to small battery packs. HeThe psychiatric Wyss Institute’s disorders, suite seizures, of machining and early-onset tools Alzheimer’s disease. “I thought to myself,explains that elderly people often sufferincludes ‘There’s 3-D no printers first aid (one for this,’ of which ” Parker is shown says. at If the men had suffered a broken limb, he could havefar tied right) a splint, that make but he three-dimensional knew there was objectsfrom poor balance when the nerves in theirno way to immediately stop the cascade of damagingbased chemical on computer-generated events happening drawings. those soldiers’ This brains.Cancer-FightingSo he went back to his lab to find oneFactory feet lose sensitivity. The insoles producewide himself. view is a composite of seven photos.vibrations that override those effects.Bioengineer David Mooney has packed a cancer-fightingThe solution Parker hit upon is a “brain on a chip,” a model of the traumatized brain that is Thefactorykey to makinginto whatthemlooksworklike awastabletnotofaspirin. With this new technology, he aims to improve treatment of melanoma, a deadly skindecades first step since, toward his understanding work has proven the effects of TBIs and how to halt them. To replicate the braincancer that can claim up to 85 percent of patientssearchingdiagnosedforafteranmetastasis.ideal vibrationTo start,frequency,otherwise.in miniature,He hasParkerdemonstrated,and his team startedforwith an elastic substrate about the size of a fingernail,Mooney’s team members biopsied a mouse tumor, but isolated recognizing some of how its proteins, complex and systems loaded inthen added a layer of cells on top to mimic networks of blood vessels in the brain. To replicateexample,the traumaticthat exertingeffects ona mechanicalvascular tissueforce them into the tablet, a biodegradable plastic device nature—like so porous that weather, it is 90 for percent example—respondair. Theyfromon an a cell improvised can activate explosive cell device, signaling.also filled the tablet with GMC-SF (granulocyte macrophageParker andto random colony-stimulating signals in the environment.factor), aninflammatory protein known to attract immune cells.At his the team first used committee a high-speed meeting motor to in stretch Cambridge,the elastic Massachusetts, substrate by Ingber one-fifth found of an himself inchBiomedical engineer James Collins, whoThen they implanted the tablet under the mouse’s skin. As expected, GMC-SF triggered ared alert, attracting immune cells that flooded theinventedtiny device.theOnceinsoles,inside,knewthesethatimmunethe actcellssurroundedin just a fewbymicroseconds,other scientiststhenbreakingreleasecame in contact with the tumor proteins and learned of walking to recognize is itself them a as complex well. Before system—a too long,it. When they analyzed the samples of theboundaries—physicists dynamic interplay of the ground, the walker’ssubstrate about 90 minutespublishingcontents of the tablet, including the trained immune cells, were trafficked to the lymph nodes,later, theyin biology found no journals, evidence biologists of increased in cell physicsbiological garrisons that help the body recognize anddeathfootwear, fight germs. the countless Once ensconced nerves that inside, enervatethe trained immune cells taught naïve counterpartsor even simple tearing. But they did findthetofeet,recognizeand thethebraintumorthatandgovernsattack. “We’republications. The group resolved to form atheable to shuttle millions of cells through this device, generating a very potent immune responseresearch that the center stretched that cells not were only hypersensitivetolerated but against the cancer cells,” Mooney says.process. Suspecting that a person’s gait couldalsotoencourageda protein thatthepromotessame kindconstrictionof interdisciplinarythe weather, Collins tried delivering randomofIn 2009, Mooney reported that the device led be just as responsive to random signals asblood vessels. To Parker, the results suggestthat headsensibility,traumaandkick-startswhoseaideaschemicalwould be to a complete regression in 40 percent of miceinspired chain of by events the now-burgeoning leading to a narrowing knowledge with metastatic melanoma. Yet the projectandpulses to elderly subjects’ feet. Sure enough,might have stalled if not for the Wyss, whereabout reshaping how nature of blood builds. vessels in the brain.the signals worked. The sensitivity of theMooney has been working with collaboratorsto develop efficient and low-costSwiss-born Over time, Parker billionaire speculates, Hansjörg the effect Wyss,nerves in the subjects’ feet was so thoroughlya HarvardcontributesBusinessto longer-termSchoolconsequencesgraduate, liked manufacturing techniques and to prepare restored that they were able to walk with thesuch as depression and a wide variety ofthe balance of a typical 20-year-old.neurodegenerativeidea so much thatdiseases.he donated the single the cancer-fighting factory for humanlargest Parker gift in hopes Harvard to eventually history, use $125 the million, trials. The first tests, in fewer than aYet the shoe inserts almost didn’t happen.dozen patients, will take place at theto make “brain it on happen. a chip” to The test school drugs tapped that can Ingber haltCollins developed the basic technology overDana-Farber Cancer Institute this year.to run the process. the show. If a compound administereda decade ago and started a company toimmediately after the simulated explosionturn his prototype into an actual product.were to stop the cascade of chemicalFilled with tumor-specific proteins andIn Parker’s “brain on a chip” (top), brain cellsSole But by 2009, a foundering economy had leftevents, Searchingthen it could be used at the site ofimplanted under the skin, the porous plasticcultured on silicone form neural networksIngber an injury, and I just stop as inside a soldier a gleaming, would tie a splintdisk David Mooney developed reprograms the(bottom). Rapidly stretching the cells at highthe project in the fledgling prototype stage.500-square-foot on a broken limb. laboratory space with airy,body’s immune system to attack tumors.speed mimics mechanical blast forces.That might have been the end of it—onehigh ceilings. Standing at a black counter-more idea in the boneyard of promisingTHIS PAGE, CLOCKWISE FROM TOP: JON CHASE/HARVARD; SAM OGDEN; MATTHEW HEMPHILL/HARVARD SCHOOL OF ENGINEERING AND APPLIED SCIENCES. OPPOSITE: WYSS INSTITUTE; PHOTO RESEARCHERS/SCIENCE SOURCE36DISCOVER04.2013

Super SlidersChemist Joanna Aizenberg found the inspiration for her latest innovation in theultra-slippery leaves of the carnivorous pitcher plant. Then she improved on natureto create permanent nonstick surfaces that could keep artificial walls free of insectinfestations, prevent ice from adhering to airplane wings, and deter bacterial growth onmedical devices continually in contact with body fluids.When wet, the leaves of the pitcher plant are essentially friction-free: Insects slidedown the surface into the interior, where the plant slowly digests them. The techniqueworks in nature because rain regularly replenishes the moisture needed to keep thesurface slick. Aizenberg knew there was no use replicating that trick: An artificialmaterial that needs to be refreshed with new liquid to remain friction-free would havelimited value. Instead, Aizenberg needed to find a way to lock lubricants in place.Toward that end, she tested several candidate materials and finally selected two: aTeflon and an epoxy resin, both highly porous. She then poured a series of samplelubricants onto small sheets of each of the porous materials. The lubricants seeped in,with a bead of liquid clinging to the surface of each pore. Next, she used an air gun toblow away the excess liquid, leaving a smooth, liquid surface. Lab tests revealed thatblood, grime, oil, and ice all rushed freely off each locked-in liquid withoutdisplacing any of it. The particular lubricant did not matter, and neither did her choiceof substrate. The surfaces also self-healed: When Aizenberg cut through the center, theremaining lubricant rushed in and filled the new gap.Aizenberg is now working with the Wyss Advanced Technology Team to find the firstapplications for her invention, dubbed slippery-liquidinfusedporous surfaces, or SLIPS. One of thelubricants they tested is FDA-approved for contactwith blood, so they are exploring the possibility ofusing the material in blood transfusions and medicaldevices—including Ingber’s sepsis device.The slippery-liquid-infused porous surfaces (SLIPS,right) was inspired by the pitcher plant (inset), whoseslick leaves capture insects and escort them to awatery demise.but unfulfilled inventions. But when Collinsjoined the Wyss in 2010, Ingber encouragedhim to revive the project. Working withthe institute’s Advanced Technology Team,composed of industry veterans, Collinsimproved the inserts’ comfort and reined inmanufacturing costs. Now, the inserts havemorphed from monstrosities resemblingorthotics for Andre the Giant into a sleek,small form. They are about to enter a clinicaltrial, and if successful, they could be soldsoon afterward.Not all Wyss inventions are so readilyidentifiable. The next contraption thatstops Ingber looks mundane enough, with asquare base, a smartphone-size LCD screen,a pair of red plastic knobs, and a few docksfor blood collection tubes. He removes halfof the rounded, plastic top to reveal a farmore complicated interior structure filledwith valves, motors, and electronics. Thisinvention magnetically pulls pathogens outof a sample of blood to diagnose sepsis, adeadly inflammatory condition caused by arange of bacteria but also fungi and viruses.Sepsis infections kill more than 1,400 peopleworldwide every day. Normally it takes daysfor doctors to identify the causative pathogenby growing it in culture. And until theyknow the precise cause of the problem, theycan’t choose the appropriate treatment.The device in front of us borrows a toolof the human immune system: moleculesknown as opsonins, which bind to pathogens,marking them for destruction. Theopsonins inside this device are geneticallymodified variants of naturally occurringones, each one stuck to the surface of amicroscopic magnetic bead. When infectedblood courses through the machine, theopsonins latch onto pathogens. Magnetsbuilt into the device then pull on the beads,washing them out of the blood, pathogensin tow. Finally, an internal microscope scansthe filtered pathogens, enabling scientiststo identify the culprit or culprits so they canprovide speedy treatment.The magnetic beads were Ingber’s idea,a remnant of work he’d begun at Yale. Amember of the Advanced Technology Team,Michael Super, is an expert in opsonins, sohe took charge of genetically modifying themolecule to make it more efficient. Even thenuts and bolts of the machine can be tracedback to Wyss production lines. Ingber snapsout a chamber that holds the blood andother fluids, explaining that it was manufacturedon a 3-D printer a few steps away.The device excites Ingber not only becauseit is his brainchild. From the tour, it is clearthat he is proudest of the inventions that areedging out of the lab and into the world: Theinstitute’s true measure of success, he says,will be the companies started and technologieslicensed over the next five years.Ingber is confident the Wyss will succeed.“We’ve built a new model for innovation,” hedeclares, that should produce technologysolutions “at an unprecedented rate.”Gregory Mone is a regular contributor to DISCOVERand author of the novel Dangerous Waters (2012).(#76190) Copyright 2013 by Discover Media LLC. Reprinted with permission from the April 2013 issue of Discover.This PDF is authorized for electronic distribution and limited print distribution through March 18, 2014.