Cancer is a leading cause of death, and many cancer treatments exhibit substantial toxicity despite minimal efficacy; we invented "high-affinity SIRPα variants" that bind cancer cells and stimulate attack by patients' own immune systems. By themselves, the SIRPα variants produce no toxicity to normal cells, but when combined with tumor-specific therapeutic antibodies, they exhibit remarkable synergy by stimulating immune cells called macrophages to engulf and destroy cancer cells.
This invention is a material based structured bioactive interface that enables a new generation of biomedical implants to directly interact with the human body for long-term functionality. The interface is easily tunable and biologically programmable with broad applicability giving rise to new therapeutic options and cures for debilitating diseases, thus increasing patient survival and improving their quality of life.
The PrestoPatch Integrated Electrode System allays the two major shortcomings of cardiac arrhythmia treatment: 1) Difficulty in switching the shocking vector (path the shock takes through the body) between shocks and 2) Difficulty in applying standardized external pressure to the patches to reduce transthoracic impedance (resistance to the electrical shock). The PrestoPatch system saves lives by solving these problems via two separate components: 1) The Tri-Patch, a disposable three-patch electrode that allows for a instantaneously switchable shocking vector 2) The PrestoPush, an ergonomic, hand-held pressure applicator that can quickly reduce transthoracic impedance on all electrode patches.
The ChemoPatch is a low-cost, electronic patch-based system that facilitates home-based chemotherapy which has not been extensively implemented because of the need for reformulated drugs and the inability to deliver complex treatment regimens. The ChemoPatch solves this problem through the automated delivery of soluble medication and will allow high-quality home-based cancer care to become a reality.
The Mechanical Leech is a medical device that will replace biological leeches in post-surgical treatment of tissue reattachment patients; alleviating venous congestion. The device will greatly improve controllability, patient appeal, and convenience while lessening the costs associated with live leeches.
Synthetic Hollow Enzyme Loaded Shells offer a versatile therapeutic strategy based on hiding and protecting otherwise immunogenic non-human enzymes from the immune system and their delivery to the target. This simple yet effective approach can potentially be applied to the majority of cancers including blood cancers, solid tumors, and metastatic lesions with application-specific modifications.
Silver-based inks are the heart of the printed electronics industry but they are difficult and expensive to manufacture. "Reactive silver inks are particle-free, can be patterned through fine nozzles, and are extremely simple to make resulting in high yields and increased performance for lower cost.
This invention enables electronically controlled internal combustion engines to operate effectively on fuels of different physical and chemical properties. The state of the art technology autonomously readjusts engine systems based on a combustion sensor to achieve goals in power, fuel economy, and reduced emission.
The Hi-Impact Shoulder Stabilization Brace is a self-applicable, low-profile brace designed for athletes who have experienced an anterior shoulder dislocation. The brace provides compressive support to the glenohumeral joint during activity to aid in prevention of secondary dislocations while still allowing athletes to perform at a high level."
A thin-film is a flat, conducting, and transparent architecture that is essential to the fabrication of electronic devices such as solar cells, transistors, and sensors. This invention is a universal and green solution to thin-film deposition that leads to high quality and large scale continuous coatings of organic and inorganic electronic materials in a matter of seconds.
The Centrifuge Chip uses cutting-edge microfluidic technology that can perform all of the operations attributed to a benchtop centrifuge, including high-throughput cell concentration, size-based cell sorting and solution exchange. This centrifuge-analogue technology offers an automated and rapid solution for the isolation of viable circulating tumor cells from peripheral human blood, which may be clinically useful as a blood-based biopsy test.
Ablation is an increasingly common way to treat cancerous lesions; however, it frequently requires a spacer to protect surrounding healthy tissue in an operation called hydrodissection. To prevent this spacer from flowing away during the procedure, this team developed a thermoreversible fluid that is injected as a liquid and forms a solid gel at body temperature, providing stable protection to healthy tissue.
Harvard-MIT Student Invents Humanized Mouse for Drug Development
By Marlene Taylor
Alice Chen has built a better mouse.
Since she was a girl, all things living fascinated her - from plants to pets. In science classes, she marveled at tiny pumping hearts, bean-sized kidneys, and seemingly never-ending strings of intestine. She wanted to be a doctor, or so she thought.
But Chen had other interests as well. The engineers in her family imbued her with an appreciation for tools - designing and building the right instrument for each job. When she entered college a new field - bioengineering - had just emerged that would allow her to combine her favorite interests.
"To me that was just the perfect blend of what I grew up wanting to do and [how] I saw myself contributing to the world," she says.
Chen is enrolled in the Health Sciences and Technology doctoral program administered jointly by Harvard Medical School and the Massachusetts Institute of Technology.
Now, after six years of graduate research, the 29-year-old biomedical and tissue engineer is the principal inventor of a "humanized" mouse that can harbor human liver cells in its body.
To a young person, Chen would explain her work by saying, "I give mice human parts so that new drugs can be tested on mice before they are tested on people like you and me." To the rest of us she simply says she"s a tissue engineer. The cells she implants in mice react to drugs as they would in humans, enabling researchers to determine if a drug is safe for human patients.
Chen designed an encapsulating device made of a watery substance that solidifies into the shape, size and consistency of a soft contact lens. Embedded with human liver cells, the device is implanted into a mouse's abdomen. It is engineered in such a way as to maintain human liver cell functions, recruit blood vessels from the mouse's vascular system and integrate with the mouse's circulation. The encapsulating process protects the liver cells from the mouse's natural immune defenses.
"Liver cells are really hard to culture in lab settings," says Chen. "Once they are extracted from the body they rapidly die."
The liver is the body's first line of defense against toxic substances and takes the brunt of unsafe drugs. Pharmaceutical companies spend upwards of $1 billion and 10 years to get one drug on the market. After undergoing years of animal trials and initiating human trials, close to 90 percent of drugs fail.
A mouse with human cells to test drugs allows researchers to know early on if a drug is damaging to the liver. Pharmaceutical researchers can then halt drug development before unsafe drugs get into the hands - and livers - of patients. This saves years in time, millions of dollars, and human lives.
Laboratory mice aren't cheap. To do the kinds of studies where cells are implanted in mice, they must be immune-deficient. Maintaining these mice is extremely laborious, time-consuming and costly. Chen can use a normal laboratory mouse as a host for her device.
Chen's humanized mouse clears the path for other kinds of liver research, such as treatments for diseases of the liver.
Cell culture models in the laboratory are useful for early detection of liver damage from drugs, but they cannot provide information about whole body responses the way animals can. Chen's mouse makes that possible.
By Jennifer Welsh
Plastic balls, plaid, Ramen noodles, and Romeo and Juliet. Erez Lieberman-Aiden sees the genome very differently than the rest of the world.
He gained this view while working on an immunology-based project. He started wondering if the genome folding that creates antibodies might be occurring elsewhere, and if these interactions might affect gene expression.
"There are some big gaps in our understanding," said Lieberman-Aiden, currently a research fellow at Harvard University. "Between the scale of about 100 bases and about 100 million bases we have a very limited knowledge of how it is the genome is folded."
The genome is essentially a polymer - a long string of repeated bases. At the base pair level two strings of bases wind into a double helix, which folds around structural proteins. We also know how chromosomes, huge chunks of hundreds of millions of base pairs that make up our genome, are arranged, but the levels between are a scientific grey area.
Figuring out genomic interactions across these distances could explain how the genome can create such a wide variety of cells in our body. "It has something to do with the regulation of this information - how it is accessed - what is turned on, what is turned off." said Lieberman-Aiden. "Our work has actually shown that that [regulation] is intimately related to how the genome is folded."
To understand this folding, Lieberman-Aiden and his teammate, Nynke van Berkum, approached the genome as if it were the text of Romeo and Juliet written out one letter at a time on a huge noodle. If you swirl that noodle in a bowl, like chromosomes in a nucleus, many different sections come into close contact.
To identify these touching sections, they froze the strand (be it noodle or genome) where it was, shattered it, glued it back together and then "read" all of the pieces, looking for the out-of-order sections. For example you might see a strand where "Two households, both alike in dignity" connected with "and Juliet is the sun!" instead of, "In fair Verona, where we lay our scene." This would mean those two sections were interacting across long stretches, because they were out of place when reconnected.
When the researchers analyzed which sequences within a chromosome were interacting, they could see they formed plaid-like patterns of compartments. The red compartments had more interactions and more activity, while the blue compartments had fewer interactions and few markers of activity.
This interaction data showed something interesting; at the million-base level the data didn"t fit accepted polymer folding models. The traditional theory, a tangled mess called the equilibrium globule, just wasn"t possible. The team found that a structure called the fractal globule, which had never been observed before, fit their data better. It's just as dense as the equilibrium globule, but unknotted for easy access.
Future work includes studying even smaller regions of interaction within the genome. They are also hoping to study different cells during differentiation to see how the genome changes conformation.
Probing the Singularity
Melding man and machine at the nano-scale
by John Motsinger
Bozhi and Tzahi. Their names alone conjure up images of twins in a circus act, but the two men are up to something even more bizarre. They work in a world of microscopic mystery, at the interstices of the digital and the biological, where the human ends and the machine begins.
Bozhi Tian moved from Shanghai six years ago to study chemistry and materials science; Tzahi Cohen-Karni moved from Israel five years ago to study applied physics and engineering. In a Harvard University nanotechnology research laboratory, the pair has developed impossibly small semiconductor probes that can record detailed electrical activity from within a single cell.
The current standard for making cellular recordings relies on a relatively blunt needle that sucks to the cell membrane to listen in from the outside. The glass needle, known as a microelectrode or patch clamp, contains an ionic solution that responds to changes in the cell's internal electrical signaling as membrane channels open and close.
In contrast, the tip of Tian and Cohen-Karni's nanowire device is one hundredth the diameter of a microelectrode and coated with a layer of lipids, which allows it to slip inside the cell membrane to record electrical signals more directly. Using a transistor that’s built into the silicon nanowire, the device can register changes in electrical potential as small as just a few millivolts, all without disturbing the normal response of the cell.
For Tian, the challenge was synthesizing silicon nanowires bent at just the right angle to enter cells easily while still forming a complete electrical circuit. By carefully controlling the temperature and pressure of precursor gases inside a glass tube furnace, Tian was able to reliably produce successive 120-degree kinks during the nanowire growth process. Changes in the flow rates of different gases, called dopants, gave rise to internal conductance changes that produce a tiny functional region at the probe tip. It's this section, the "field effect transistor," that’s capable of measuring changes in electrical potential in the surrounding environment.
To record from living tissue, however, Cohen-Karni had to devise a new method of positioning the probe into target cells. Though each nanowire probe is tiny, with hundreds of probes forming contacts in an area half the size of your pinky nail, the overall device is part of an integrated circuit that is relatively large. So Cohen-Karni came up with a way to invert a cultured substrate of cardiac cells and position the complex on top of the probe device using a micro-manipulator. That way the bigger device chip remains fixed while the smaller cell substrate is free to move in all three dimensions.
The innovation has already paved the way for designing cyborg cells from silicon wafers that can track the contractions of individual muscle cells. What lies beyond is implanting neural chips and nano-scale pacemakers into the brain and heart - the seamless fusion of the body's own circuity with manufactured hardware.
Inventing a Legacy
By Joe Giesy
Since he was a child, the gears inside Mark Jensen's head have been constantly rotating.
"It was really clear he had an engineering mind," his father, David Jensen, said of his son who skipped eighth grade and had an associate's degree before graduating high school.
As an adult, Mark Jensen is using that engineering mind to work with a completely different set of gears.
About 15 years ago, his father invented a lightweight, composite lattice pole structure called IsoTruss and, more recently, Mark Jensen invented a machine to braid and weave fibers into this structure that could potentially take the place of steel and wooden beams.
Mark Jensen said IsoTruss could also be used in the production of motor vehicles and airplanes as a cheaper, greener solution to current models because the design of the composites makes it lightweight and more fuel-efficient.
"It's going to be lighter weight, it's going to be stronger [and] the carbon footprint is going to be smaller," Jensen said. "A lot of people try to pitch 'green' or whatever, but the product really is truly greener than a lot of things we use now."
Along with Aaron Howcraft, co-creator of the machine, Mark Jensen has founded Altus Poles LLC and won many business competitions already. They partnered with a company called Novatek to maintain a home for their company and help buy machining supplies cheaper.
David Jensen, a professor at Brigham Young University, designed the IsoTruss structure when Mark Jensen was a child and now acts as an adviser for him in some of the business and invention competitions he entered before graduating from BYU last April.
"As his adviser, he's the perfect student to work with because he's responsible, he's creative, he's smart and he gets things done," David Jensen said. "As his father, I'm very proud, and I'm very excited for what he's doing with the IsoTruss, which is something I've devoted a lot of my life to."
A deal between Altus Poles, BYU and Novatek allowed David Jensen to become a consultant for his son's work. He said he enjoys working side-by-side with him and is proud he is the one who will make IsoTruss commercially available after years of frustration trying this same feat himself.
The machine is made up of a series of gears that rotate bobbins around an axis and switches that allow the bobbins to move from gear to gear, braiding them into the composite material that makes up the structure. The whole system is run by computer software Mark Jensen helped to develop.
Howcraft said Mark Jensen's focus was always to make the business successful and they have both taken big risks to get the machine running and their company off the ground.
David Jensen said he is nervous for his son because he has seen companies fail, but he has high confidence in his son.
"When he says 'I can do this,' I know he'll learn how to do it and do it right," he said.
Left Behind After Surgery
Researchers work to produce a surgical sponge that the body can absorb
By Charli Kerns
No patient enjoys waking from a surgery only to realize something was left behind. Likewise, no doctor takes pleasure in reopening the patient to retrieve that missing something. These fears are not unfounded. Surgical sponges - cotton sponges that absorb liquids from a surgical site - have a lengthy history of ending up on the wrong side of the stitches, with an average 5,000 cases a year. Doctors have even developed a special term for it called gossypiboma.
Doctors use several techniques to avoid gossypiboma, which include having one individual solely for counting the equipment before and after surgery. Some manufacturers embed a strip of radio-opaque material into the sponge, which can pinpoint the sponge's location. However, even though these techniques often work, the potential problem remains. The sponge is still inside the body.
Researchers Devon Anderson, Jonathan Guerrette, and Nathan Niparko from Dartmouth University are working on a solution to the forgotten sponge problem. Since the fall of 2009, the team has been trying to produce a bioabsorbable sponge, one that the body can absorb over a short period of time.
The sponge is a product formed by mixing cellulose and alginate, both of which are oxidized, a process that transforms the chemical fabrics into bioabsorbable material. Cellulose helps form the walls of most plant and animal cells, while alginate is a biomaterial derived from seaweed.
Both cellulose and alginate are already used commercially in the hospital, the former as a hemostat for blood and the latter as a dressing for wounds. Together, they have the features necessary to create the biodegradable sponge.
"We're trying to find the right percentages, ratios, and viscosity to produce the desired results," said Anderson, biomedical researcher at Thayer College of Engineering at Dartmouth. The sponge is essentially a medical souffle. Every measurement must be just right or the end product becomes nothing more than thin white paste, which Jonathan, Dartmouth graduate student in chemical engineering, said was all they got at the beginning.
"We've come a long way since our first trial runs," said Guerrette, who works on the chemistry compositions for the research. After finding the right recipe, the team mixes the ingredients by electrospinning. Put simply, the components are spit out of a needle at a very fast rate onto aluminum foil hanging 17 centimeters away, leaving the solvent behind.
"It was incredibly exciting for us when we saw the first results of the electrospinning, and there were actually fibers on the aluminum that would peel off," said Nathan, the logistics member of the team.
The team will soon move on to work with animal model testing and see how the sponge will react to flesh. Though a commercial application may be far off, the group is starting to see the light at the end. Devon said, "To walk through the process and find a product we"re really happy with is exciting."
Designing a Smarter Surgical Drill
By Matt Dozier
"Aim for my finger."
The drill whined, its five-inch stainless steel bit penetrating bone and flesh at 1,500 rpm. Dr. Lew Schon watched as a surgical resident guided the tool through the patient"s ankle in the direction of his waiting index digit. Easing forward, the young doctor bored into the fibula, then tibia. Suddenly, the drill hit a weaker patch of bone and surged ahead, plunging toward Dr. Schon"s finger. He jerked his hand away, barely escaping serious injury.
Dr. Schon, a 20-year veteran of orthopedic surgery, wondered if there was a better way to teach novice surgeons in the operating room, so he brought his dilemma to Dr. Robert Allen's Biomedical Design Team class at Johns Hopkins University.
Biomedical engineering students Leyla Isik, Emilie Yeh, Michael Shen and Salina Khushal dove into the project, spending summer 2009 planning and brainstorming ideas for a device that could make orthopedic surgery safer and decrease the training time for new surgeons. Their solution: an "intelligent" drill that could provide better feedback to someone learning the art of surgical drilling.
The field of orthopedics, which includes skeleton- and muscle-related maladies ranging from broken legs to torn ligaments, often involves drilling to stabilize and repair damaged bones. Compared to brain or heart surgery, which take a stable environment and a steady hand (think "Operation"), orthopedic surgery is much more dynamic: limbs need to be repositioned, joints flexed, appendages rotated to find the best angle (think "Twister"). It"s a procedure that relies more on experience and intuition than technology, requiring surgeons to complete six long years of residency training.
"Orthopedic surgery is still quite low-tech," said Isik, leader of the design team. "Right now, the training is really a trial-and-error process."
In the fall, the Johns Hopkins team, now 10 members in total, started building prototypes of their invention - some more successful than others. "We"re not the most skilled electrical engineers," Yeh admitted. "There were a couple of fires, and lots of smoke." Team members worked on the project for the rest of the year, testing their designs and getting feedback from residents at Union Memorial Hospital, where Dr. Schon, one of the team's sponsors, practices medicine.
By spring 2010, their perseverance had paid off. Their invention, a small box that can clip to the back of any standard surgical drill, uses lights to tell a surgeon if the drill veers off its intended course. It can also trigger an alarm or even shut off the power if the drill speeds up too quickly, making it a tremendous learning tool in terms of visual feedback and safety.
Isik said she hopes the device, currently undergoing further development by Bioactive Surgical, will be able to gain support as a training tool in a surgical community that is notoriously suspicious of technology, based on its small size and relatively low cost - estimated at $3,000, compared to $10,000 camera-tracking systems.
"We would love to see it in the O.R.," she said. "This whole experience has been amazing."
Geoffrey von Maltzahn turns what may be a new page in nanomedicine with his method of using a pair of nanoparticles that work together in an innovative way to increase the effectiveness and lower the side effects of existing cancer drugs. In his approach, one set of nanoparticles lodges in tumors and generates numerous targets for a second set of nanoparticles that deliver anti-cancer drugs. This process of signal amplification differs from traditional combination therapies and may make it possible to target such drugs much more directly than currently possible, potentially allowing higher doses to reach tumors while sparing healthy cells.
Powerful cancer-killing drugs are well-known to science and widely used in clinical medicine, but since these drugs are also highly toxic to healthy cells, targeting drugs specifically to tumors has been a major focus in cancer research. Of late, much of this drug-targeting research has looked at using nanoparticles to carry the drugs to tumors. A major challenge, however, is that cancer cells, and the tumors they may form, have finite numbers of targets to which nanoparticles can attach - and since a given nanoparticle can carry only a small drug payload, this limits the amount of drug that can be delivered.
Tumors have a high demand for nutrients and oxygen, and as a result have many blood vessels supplying them. Von Maltzahn"s first nanoparticle targets the tumor blood vessels and in doing so, causes local bleeding. The bleeding prompts the body to turn on clotting factors in the area. Then, the second nanoparticle comes in, programmed to be attracted to the activated clotting factors, and delivers a cancer drug. Since the body responds to an even small amount of bleeding with a flood of clotting factors, this process dramatically increases the number of targets for the drug-carrying particles. In essence, the first nanoparticles find the tumors and then recruit the second nanoparticles from circulation by harnessing a natural chain reaction.
Von Maltzahn has compelling data demonstrating efficacy in mouse experiments, and hopes to continue refining his approach to make it particularly effective in delivering drugs to patients with highly metastatic cancers, and other diseases.
Raised first in Arlington, Texas and then Fairfax, Virginia, Von Maltzahn, 29, received degrees from both MIT and the University of California, San Diego before beginning his current work on a Ph.D. in medical engineering and physics. He was influenced when he was young by his interest in art and his observations of the natural world around him. He says, "It was a fun process of observation, interpretation, and creation. Today, I use many of the same processes in the medium of biologically-inspired engineering."
Harris Wang was a student in the lab of George Church, a researcher well-known in the world of genetic sequencing for his attempts to make genetic sequencing faster and cheaper. Church was long interested in creating faster tools for cell programming, and discovered that Wang was willing to take on the challenge. Wang knew that cell programming was still a slow and hands-on process. So he developed a protocol designed to permit faster cell programming, and then put together hardware and software to automate it. He calls the approach MAGE: Multiplex Automated Genome Engineering.
To demonstrate, Wang engineered a strain of E. coli bacterium that produces lycopene - a red-colored antioxidant, abundant in tomatoes and that may be linked to reduced rates of prostate cancer. Wang added the genetic recipe for lycopene to the bacterium's chromosome. Then he used his MAGE approach to evolve a strain of the bacteria in which production of lycopene was highly efficient. In a more traditional approach, researchers painstakingly isolate, snip apart, reassemble, and reinsert individual genes.
Wang, on the other hand, quickly produced billions of mutations - far more than he would have had time to create by hand. Wang believes that his technology will allow bioengineers to produce customized microorganisms much more cheaply and quickly than possible before. Such engineered microorganisms might be used to produce a wide variety of useful compounds, such as antibiotics, biofuels, and chemotherapy drugs.
Wang, 26, is currently working towards his doctorate in biophysics. Born in Beijing, Wang moved with his family to the U.S. at age nine and grew up in Salt Lake City. He remembers as a child when his aunt made him write out thousands of Chinese calligraphy characters. If he thought about writing a thousand characters, it was daunting, but if he thought about writing characters in sets of ten, then it wasn"t. He says, "Science is often this way, too. We may look at a big scientific challenge and get intimidated by the size, scale, and scope, but if we boil it down into smaller components, then we can make progress in a reasonable manner."
Stephen Diebold presents an improved pointing stick for use by people with quadriplegia and other disabilities that prevent them from using their arms. Pointing sticks are used to type, operate cell phones, and otherwise manipulate objects. Existing pointing sticks are gripped in the user's teeth or mounted, helmet-like, on the user's head. Either approach presents problems: a mouth-held pointer prevents the user from speaking and a head-mounted pointer requires assistance to put on or take off.
Diebold's pointing stick is designed to be donned and doffed with a shrug of the user's chin. He came up with the approach after spending time with then law-student Jonathan Ko, who has quadriplegia. Diebold said, "I saw that to Jonathan, the pointing stick was his arms and hands, and he had to ask somebody every time he wanted to use his hands - that seemed absurd to me." By attaching the pointing stick to a cup which is in turn attached to a strap that loops around the user"s neck, the user is able to freely engage the pointer as he wishes.
A native of the Chicago suburb Rolling Meadows and a graduate of William Fremd High School, Diebold, 21, is now majoring in industrial design. He finds himself drawn to the field for its blend of research and art, since products must not just be functional but also able to instill enjoyment and pride in the user. Upon his graduation, if Diebold doesn"t find himself a part of the industrial design field, he will be pursuing computer animation to focus on rendering products or architecture interiors. For the moment, he"s proud of the fact that he has a U.S. patent pending for his design of The Drop Point.
As part of a capstone design course for Dartmouth's engineering program, Phil Wagner, Lindsay Holiday, and Dana Leland tackled a problem: to reduce arsenic found in groundwater to safe levels, with a cheap, reliable device made of materials locally available in rural Nepal.
Arsenic naturally leaches out of the rock underlying much of Nepal, so the groundwater there typically contains up to 200 parts per billion (ppb) of arsenic. The World Health Organization (WHO) standards for drinking water call for no more than 10 ppb arsenic, and WHO considers arsenic in drinking water an "urgent problem" in Nepal and neighboring areas.
The team developed a way of using electrocoagulation - a process employed in the large-scale water treatment plants of many modern cities - in a system radically downsized to fit into three five-gallon buckets. Water to be treated goes into the first bucket where the students induce electrocoagulation by sending a simple electric current through two steel plates in the water. Iron precipitates are released. These iron particles bond aggressively with the arsenic that exists in the water. This newly-reacted water is then poured into a second bucket of clean sand, which has a hole in the bottom and sits over a third empty bucket. The sand collects the iron-arsenic particles and arsenic-free water collects in the bottom bucket. When the team tested the device with water contaminated with 200 ppb arsenic, the output water contained under 1ppb arsenic - well under the 10 ppb level considered safe for drinking.
Wagner, 22, who grew up in Fogelsville, Pennsylvania and graduated in Spring 2009 with his engineering degree, is currently spending a year teaching high school in the Marshall Islands. Upon his return to the U.S., Wagner plans to continue graduate studies in engineering. As he says, "Engineering balances both a science aspect and a human aspect, which makes it endlessly interesting."
Holiday, 24, spent time growing up in both Teec Nos Pos, Arizona in the Navajo Nation and Phoenix. As a recent environmental engineering graduate, she looks forward to her immediate work with the Energy Efficiency Division of Southern California Edison. Looking forward several years into the future, Holiday says, "I would like to own a business on the Navajo Nation and encourage building sustainable communities."
Also a recent environmental engineering graduate and a Baltimore native, Leland, 22, is now a project manager at Eaton Corporation in Wisconsin, participating in a fast-track leadership program. Leland found work on the capstone engineering project very rewarding, commenting, "I hope our work can help bring clean drinking water to people in need in third world nations such as Nepal, Bangladesh, and Cambodia."
When Paul Podsiadlo looks at natural materials such as seashells, bones, or teeth, he sees amazing structures. He notes how these seemingly simple yet microscopically quite complex structures have evolved over millions of years into some of the toughest composites, and as he looks at them, he tries to understand their structure and how they function with the hope of mimicking their properties for the development of the next generation of advanced materials. It is this same thoughtful approach to all problems in his research that encourages Podsiadlo and that makes his research exciting for him.
For his University of Michigan research, Podsiadlo knew he wanted to create high performance materials by using nanotechnology as his tool. His innovation is "plastic steel," a transparent plastic sheet that is ultra strong, with remarkable properties approaching the values of steel and its alloys. To create his composite plastic, Podsiadlo begins with nanoscale materials, actually clay nanotubes that individually are extremely strong. One of his challenges was determining how to transfer the nanoscale mechanical properties to a macroscale end product. Podsiadlo uses a layer-by-layer assembly technique to alternately deposit nanometer-thin layers of clay nanosheets and polymer, ending up with a product comprised of hundreds of layers. The structure of the final product resembles that found in the seashell: the nacre.
Podsiadlo looks forward to the broad impact his innovation could have, especially in the military, aviation, medical, and energy sectors. He envisions his structure being used for anything from body armor to biomedical coatings. In fact, research for the project was initially funded by the U.S. Defense Department and the National Institutes of Health.
Podsiadlo, 30, was born in a small village in Poland where he always enjoyed the sciences and math in school, often helping his teacher grade math exams. At 17, he came to the United States and graduated from Bridgman High School in Bridgman, Michigan in 1997. As he studied at a local community college, he found that his most interesting classes were in chemistry. In fact, he remembers an experience in the lab making a sample of common acetylsalicylic acid, also known as aspirin, as a particularly positive moment that piqued his interest in the topic. Unsure whether his English skills would allow him to succeed at a school such as the University of Michigan, Podsiadlo took a chance and applied and was thrilled when he was accepted.
In 2002, Podsiadlo received his bachelor's in chemical engineering, in 2006, he received his master's, and in 2008, he received his Ph.D. During his doctoral research in 2006, Podsiadlo was granted a five-year fellowship from the Hertz Foundation, supporting his research at Michigan. Now a U.S. citizen, Podsiadlo lives in the Chicago area with his wife Aneta, who is expecting their first child in December. Currently he is a Frank Willard Libby Postdoctoral Fellow at the Argonne National Laboratory's Center for Nanoscale Materials where he continues his research in nanotechnology. Podsiadlo admits, "I really enjoy research, every aspect of it. I can"t just go home and switch off. My wife probably knows more about carbon nanotubes and clay nanosheets than she wishes she did."
While performing his clinical rotations at a large hospital, Timothy Lu, a Harvard Medical School and MIT student, was bothered by the infectious outbreaks he witnessed in many patients. The unexpected infections would cause lengthened hospital stays, additional treatment, or both, resulting in increased healthcare dollars being spent. Lu remembers, "That experience drove me to look for a solution to this problem."
Lu knew that antibiotic-resistant bacteria are usually treated with stronger and stronger antibiotics, leading to subsequent decreases in the antibiotics available for the treatment of future infections as resistance continues to evolve. He also knew that very few new classes of antibiotics have been developed within the past few decades, partly due to the large cost associated with modern drug discovery. Working in the new field of synthetic biology, Lu created engineered bacteriophages - viruses that infect bacteria - which work in conjunction with existing antibiotics to make them much more effective against bacteria.
In addition, Lu realized that bacterial biofilms are capable of causing long-term infections, not just in hospitals but also in food-processing and industrial settings. Biofilms are bacterial communities that live on surfaces and produce protective coatings to make themselves highly resistant to antimicrobial treatment. Common tactics to deal with biofilms involve physically removing and replacing infected items or using harsh chemical treatments. Instead, Lu engineered bacteriophage to produce enzymes that break down the protective coating surrounding biofilms, enabling deep penetration into biofilms and increased killing of bacterial cells.
Captivated by research, Lu is hopeful that his inventions will have a positive impact on society and health. In addition to finding success with his work, he also enjoys collaborating with others to improving patient care.
Born in Stanford, California, Lu, 27, spent his early years growing up in New York and then moved to Taiwan, where he graduated from high school. His parents continue to live in Taiwan, where his father founded and runs, along with his mother, Etron Technology, an integrated circuit design and production company. Lu recalls that when he was young, his father was involved with advancing state-of-the-art technology in the semiconductor industry as an engineer at IBM. Lu likens the emerging field of synthetic biology to the early and revolutionary days of the semiconductor industry and is inspired by the parallels he sees between the two fields.
A 2003 graduate of MIT with his bachelor's and master's degrees in electrical engineering and computer science, Lu is a student in the M.D./Ph.D. program at the Harvard-MIT Division of Health Sciences and Technology. He received his Ph.D. in February 2008 and expects to receive his M.D. in 2010. As for his plans upon graduation, he says, "My heart really is in research. I"m not sure if it will be academia or industry, but I want to stay involved in research and make an impact on the world."
As a senior thesis project at MIT, Schroll explored a fascination he has had for some time with spherical vehicles. After a broad investigation into prior research on the subject, he found that previous design concepts have significant limits in their ability to overcome obstacles or inclines, and decided he would try to address these limitations. Through months of brainstorming, he conceived of a novel solution that uses gyroscopes to store and dispense angular momentum to aid in climbing hills, obstacles, and stairs.
Schroll came up with the idea partly by playing with a toy gyroscope. "I saw how gyroscopes can behave in ways that seem to defy gravity as a result of the principle of gyroscopic precession. I applied this principle to a spherical robot to allow it to also appear to defy gravity," he said.
Schroll believes that a spherical vehicle has many advantages over an ordinary ground vehicle because of its round shape. It cannot be turned upside down since every orientation is right side up, and it has no exposed points of weakness. All components are protected inside a spherical shell that could be armored and possibly sealed to give it amphibious abilities. Despite these advantages, limits in the performance of previous designs have prevented spherical vehicles from being useful for most applications, but Schroll hopes this invention will change that. He imagines his spherical robot having many potential uses including surveillance, reconnaissance, and disaster zone assessment especially in situations where conditions on the ground may not yet be safe for people. He envisions being able to air drop a fleet of sphere robots into a location and have them work together yet autonomously to gather information. He says his robot would also be appropriate for planetary exploration, as well as search and rescue since its ability to climb stairs would allow access to urban environments. Schroll says that the internal flywheel mechanism could also be useful in applications such as active stability and safety in off-road vehicles.
Presently a graduate student at Colorado State University, Schroll is furthering his research on his spherical robot and the gyroscope mechanism inside. Now 22, Schroll grew up in Chatham, New Jersey, and graduated in 2004 from Chatham High School. His family currently resides in Highlands Ranch, Colorado. Schroll graduated with his bachelor's degree in Mechanical Engineering from MIT in May of 2008, and he expects to graduate with his master's in Mechanical Engineering from CSU in 2010. Schroll plans to obtain a Ph.D., and hopes to continue doing advanced research in either an academic or industrial environment. Ultimately, however, he would like to work as an independent inventor and start his own think-tank company. As he says, "I have a running list of inventions-to-be," and he looks forward to having the opportunity to pursue them.
John Dolan investigates the molecular mechanisms responsible for oral and facial pain. Dolan observes, "While in dental school I attended to patients with untreatable pain from disorders such as oral cancer." He realized that the most substantial obstacle to improved pain medication was the inability to measure oral and facial pain in experimental animals. Without an instrument to measure oral or facial pain in animals, it was impossible to test the efficacy of experimental painkillers. Dolan notes, "Diseases such as oral cancer or temporomandibular joint disorders are excruciatingly painful when patients chew or open their mouths. Therefore, the pain research community needs an instrument that measures pain in animals during the same behaviors that are producing pain in patients."
Dolan realized that gnawing in rodents uses the same muscles, joints, nerves and soft tissues of the oral cavity and face that are required for almost all oral functions in humans. He then created a device that could measure gnawing function in animals by taking advantage of an instinct observed in rodents. If a mouse is placed in a narrow tube with an obstacle at the end, it will instinctively gnaw at the obstacle to escape. Dolan"s device exploits this instinct. The device, termed a Dolognawmeter, (dolor, Latin for pain; gnawmeter referring to measurement of gnawing) automatically records the time required for a mouse to gnaw through a series of dowels obstructing exit from a tube. Upon severing the dowels, the mouse escapes from the tube. Slower gnawing indexes greater pain, providing Dolan with a way to study the effectiveness of painkillers.
The apparatus is inexpensive, compact and simple; multiple Dolognawmeters can be used in parallel to simultaneously evaluate many mice. Since mice are nocturnal, the device is employed inside a standard research cage at night since no operator observation is required. Dolan says the device has the potential to revolutionize the way that both analgesics and anxiolytics (anti-anxiety drugs) are tested. "Since confinement anxiety motivates the mouse to gnaw, a Dolognawmeter will also allow for a simple, cheap and objective method to test new anxiolytics in animals. That alone makes the device worth its weight in gold," says Dolan.
Dolan began his education in anthropology, earning a B.S. from Montana State University and an M.A. from the University of California, Berkeley. While working toward his Ph.D. in anthropology he was inspired by studies demonstrating that a person's creativity often peaks by the late twenties or early thirties. Upon learning this, he put aside his graduate work, purchased a used Tungsten Inert Gas welder from an Oakland shipyard and became an artist for five years. He says, "My greatest skill since childhood has been artistic mechanical design." In 2003 he combined his passion for material sciences and the application of mechanical principles to human problems and entered dental school. At the same time, he began research into the mechanisms of oral and facial pain. He earned his DDS in 2007 and is currently in a postgraduate program in oral and craniofacial sciences at UCSF.
Ian Cheong didn't start out in a scientific career. The Singapore native trained to become a lawyer in his home country, and ended up working at a law firm specializing in corporate criminal litigation. Some of the firm's clients were scientists, and as Cheong says, "Science looked like it was too much fun to be left to the scientists." With that, he left the world of law behind and began his scientific studies.
Once at Johns Hopkins, Cheong focused on a main problem in cancer therapy; namely, drugs used in cancer treatment kill the healthy cells as well as the cancer cells. Many cancer drugs are potent, but they are nonspecific, and there is continuous searching for ways to make the drugs more specific.
Cheong has devised a way to target cancerous tumors and release the drugs just in those areas. He begins by injecting bacterial spores into the subject which selectively inhabit the oxygen-poor areas found within cancerous tumors. Next, Cheong puts the cancer-fighting drug in lipid particles and injects these liposomes into the subject. Because the germinated bacterial spores also secrete a protein that makes liposomes fall apart, when the drug-containing liposomes are in the proximity of the tumors, the drug is released only in those specific areas.
In testing conducted on mice, Cheong was astonished at the results. One hundred percent of the mice showed regression of the tumors. In fact, Cheong recalls that the moment when he realized that the mice tumors were being eradicated as a high point of his research. He hopes his work will have a positive impact in the treatment and diagnosis of cancer.
Cheong, 33, arrived in the U.S. in September 2001 to begin his studies. He received his Ph.D. in cell and molecular medicine from Johns Hopkins in 2006. Currently, he is working on postdoctoral research at JHU, and he hopes to remain in academia while focusing on research that industry would normally classify as high risk ideas. He says, "These are the ideas that need to be explored because they have the potential to completely change how we treat cancer." He is married to Dawn Kua, who runs a nonprofit organization in Singapore.
As Corey Centen and Nilesh Patel sat in their college cafeteria at the beginning of their senior year, they discussed ideas for their final project. As they talked, they realized that even though both had been trained in CPR in high school, neither of them could really remember how to do it if faced with an emergency situation. They thought it would be great to have a device that could assist people with CPR in emergency situations and even help train them on the techniques. The idea for the CPRGlove was born.
Centen and Patel conducted research, and they were surprised to discover that a 2005 study concluded that CPR quality was well below the levels it should be, even when administered by health care professionals. Convinced that there was a real need for a device to assist with CPR, they began working on a prototype, outfitting a store-bought glove with various electronics. By the next year, their design had progressed to a custom-made glove with sensors and an LCD screen to give instructions and feedback when the user performs CPR. The glove is able to provide information on the rate, depth, force, and angle of compressions as well as the heart rate. It also speaks, providing verbal cues for the user.
What began as a senior project for them has turned into a business. Along with a fellow electrical and biomedical engineering classmate from McMaster, they formed Atreo Medical, Inc. to refine and market the device. They've been pleased to receive support and funding for working on the glove from various Canadian sources, and they are making headway in the U.S. as well.
Centen, 22, grew up in Ottawa, Ontario. Always interested in inventing as a youngster, he recalls continuously working on his own projects, even turning the dining room of his home into a mini-lab for his work. "My parents," he remembers, "were very generous." After graduating from Immaculata High School, he found things similar as a student at McMaster, where he created an unofficial lab in the corner of his dorm room. Centen graduated earlier this year with a degree in electrical and biomedical engineering and is the CEO of Atreo. The CPRGlove is an exciting project for him as he thinks about the lives that could potentially be saved. "Right now," he says, "we"re focusing on a final prototype for clinical trials, and then we"ll work on FDA approval."
Patel, 21, is from Toronto where he graduated from West Humber Collegiate Institute. He looks forward to graduating from McMaster with his electrical and biomedical engineering degree in 2008. Patel also remembers his inventiveness as a child, once using a cardboard box, a solar panel, and some LEDs to create a solar house. He sees the importance of the three main uses for the CPRGlove - to train individuals in CPR, to test their knowledge of it, and to use in emergency situations. Patel is also thrilled to know that the glove has been receiving positive attention. He notes, "After a story ran about our work with the glove, we were actually contacted by the lead researcher of the 2005 CPR study that we had researched." Patel is currently the chief technical officer of Atreo.
Craig Hashi and YiQian Zhu both know that blood vessels that clog and harden are a critical problem in the health care industry. One of the usual ways of treating clogged vessels is by using a graft to bypass the clog and restore normal blood flow. The graft is usually supplied from a vein or artery elsewhere in the patient's body.
Hashi and Zhu also know that all too often, bypass grafts can fail. They realized that another option was synthetic grafts, but these grafts also have their limitations. So, the team worked together to experiment with a new kind of graft. They take an FDA-approved polymer and create long, thin strands which are formed into a very thin mat. Then, the mat is seeded with bone marrow stem cells and left to culture. Once the cells have had a chance to grow, the mat is carefully rolled and formed into a tube. The tube - their graft - is then ready to implant as a vascular graft and as a fully-functioning blood vessel. Chances of rejection are greatly reduced because the patient"s own cells could be used to create the graft.
According to Hashi, "There are currently no tissue-engineered vascular grafts on the market. The idea of an off-the-shelf graft ready for the patient in time for surgery is exciting." He notes that it is helpful for him to step back and look at his projects from an engineering mindset. He remembers that as a youngster, it was natural for him to go into engineering because he was good at it. Not until he was in graduate school did he develop his healthy respect for biology.
Hashi, 24, of Torrance, California, graduated from South High School in 1999. His parents, Katsuo and Rumiko Hashi, also of Torrance, still own a landscaping business in the area. Hashi received his undergraduate degree in mechanical engineering from UCLA, and he is currently working on his Ph.D. in bioengineering at Berkeley.
Zhu, 31, originally from Shanghai, China, has been in the United States since 2003. A neurosurgeon by training, his expertise was instrumental in placing the grafts within the animal subjects and providing the medical knowledge needed to create the grafts. Zhu conducted all the in vivo techniques, and is looking forward to their invention being one day available on the market.
As a child, Zhu remembers times with his parents, a pediatrician and a general practitioner physician. "My parents would talk about medical things at dinner," he says. "They would take me to the hospital with them, and I began to know their world." Their influence shows, as Zhu went on to Fudan University Medical School, graduating with his medical degree in 1999. After four years working as a resident in training at Huashan Hospital, he traveled to the United States to undertake postdoctoral work at the University of California, San Francisco. Currently, he is in the bioengineering program at Berkeley and San Francisco, and he hopes to obtain his Ph.D. by 2009.
When Matt Haugland was a child in San Jose, California, he remembers that his parents gave him a small thermometer that he used to measure the temperature in different spots around his yard. Although the yard wasn't large, Haugland was fascinated by the temperature differences in the different parts of his yard. As he grew older, he became fascinated by the microclimates of the San Francisco Bay region and the reasons behind them.
Consequently, Haugland hoped to own land for the purpose of researching the microclimates on it. In 1999, he transferred from school in San Jose to the University of Oklahoma in search of affordable land. He bought a five-acre plot and installed several weather stations across it. Through his research, based on weather observations from these stations, Haugland developed a weather forecasting technique that accurately predicts nighttime temperatures.
As Haugland says, "I"m hoping that this model will help improve weather forecasts around the world." The implications of his work are broad, from helping farmers protect their crops from frost and freezing, to helping predict nighttime fog formation, the biggest weather-related cause of death in transportation.
"The idea of innovation really motivates me," comments Haugland. "Growing up in Silicon Valley, I was surrounded by a culture of finding new ways of doing things." Even as a child, Haugland thought about working with the weather, as when he planted cacti in his yard in hopes they would turn the land into a desert. Today, Haugland notes that he is often thinking about the way weather works and new ways of predicting it.
Haugland, 26, has come a long way from when he was a youngster concentrating on his backyard experiments. He is now hoping to run a successful business focused on microclimates and microscale weather forecasting. Already, Haugland has received interest internationally for his work.
Haugland attended Leigh High School in San Jose, graduating in 1997. After attending San Jose State University for two years, he transferred to the University of Oklahoma, receiving his bachelor's degree in 2001, his master's degree in 2002, and his Ph.D. in May of 2006, all in meteorology. His parents, James and Holly Haugland, continue to reside in the San Jose, California area.
Currently, 70 million people around the world wear contact lenses. Up to 20% of those people could end up contracting a lens-inducted infection. Fan Yang's strategy is to prevent infection-causing bacteria from adhering to contact lenses by coating the lenses with safe chemicals.
When Yang was just in the 8th grade, she interned in a lab. There, she worked on a project that looked for compounds that could adhere to bacteria. She was interested to discover that some compounds did not adhere. A few years later, she went to her optometrist for an eye check-up. She was warned away from contacts because of the possible risk of infection. Once she arrived at Johns Hopkins, she took these pieces of her past, put them together, and began work on her anti-adherent project using nano-techniques.
Yang, 18, isn"t always sure where her ideas come from. "Sometimes I feel like they just pop up," she says. "Sometimes I"m able to write them down. Then, I have to sort them out, read literature about them, and research." Regardless, when she is working on a problem, she is always excited when she finds a solution. As she notes, "It means I have finally done something that no one has ever done before." Ten minutes later, though, Yang finds herself at work on another problem, facing obstacles again.
When Yang was ten years old, she moved from Peking, China to Davis, California with her mother, Yan-Lei Liu, a laboratory technician at Davis Medical School. Although young, she remembers her childhood years in China. "I always like to solve problems," she says. "When I was five years old, we didn"t have air conditioning at home. So, I would open the refrigerator in the summer and sit in front of it to read my books. My grandmother finally hid and watched me, because she wanted to know why the electric bill was so high." In the sixth grade, in the U.S., she remembers becoming interested in microbiology after a school science project that caused her to examine bacteria levels before and after hand washing in order to find the reason why her mother always asked her to wash her hands before eating.
Currently studying biomaterial and nanomaterial engineering, Yang is a sophomore who hopes to attend dental school, and then eventually study for her Ph.D.
Jwa-Min Nam is a chemist, and Shad Thaxton is a physician. Together, they invented a new technology with the potential to revolutionize their respective fields of chemistry and medicine.
The two graduate students at Northwestern University created what they call "bio barcode amplified detection systems." The complex process has a simple goal: to find miniscule amounts of microscopic biological materials. Because their invention is so much more sensitive and precise than previous types of tests, it could be used to detect chemical signs of Alzheimer's disease or types of cancer far earlier than conventional tests.
Wei Gu's invention involves microfluidics, an emerging technology relying on microscopic control of liquid flows from medical purposes to chemical analysis. Gu has created an unusually simple, robust machine that acts as a miniature plumbing system, complete with microscopic pumps, valves, pipes, and mixing chambers. "I think in the future these devices will be as common as cell phones or laptops," Gu said, explaining that microfluidic machines could become powerful diagnostic tools for doctors, or allow patients to monitor their health more precisely than is possible today.
Sahin invented a dramatically improved type of Atomic Force Microscope, an exciting type of instrument capable of taking pictures of individual atoms. The AFM is used by a wide range of researchers, from people designing cutting-edge computer chips to biologists trying to learn the inner workings of cells. The AFM uses a tiny probe that vibrates over a sample, literally feeling the surface.
The ever-increasing drive to make electronic circuits smaller and smaller is increasingly frustrated by certain types of components that refuse to shrink. These students found a solution by building a novel type of micromechanical oscillator: one shaped like a dome. Their oscillator resonates like a bell in response to light or heat. The dome is tiny and can be built on a chip. That makes it perfect for a wide range of electronic applications, especially in the field of telecommunications. Microscopic domes could replace many of the largest, most expensive parts contained in cells phones, among other devices.
The trio uses light to try and control the shape of silver nanoprisms. By amending the size and structure of the tiny particles with light, they produce a product with intense optical properties - nanoparticles of different bright colors that could be used for biological labeling, inks, specialized films, and cosmetics, just to name a few applications.
Shen knew that patients with type I diabetes must receive insulin everyday because their pancreas fails to produce it. Her goal became to create a way for stem cells to release insulin in a completely synthetic environment and then be transplanted into the body to provide a permanent source of insulin. Taking stem cells from the adult rat liver, she inserted them into a growth medium that was essentially a three-dimensional scaffold. Then, she stimulated the scaffold with different growth factors, and the cells produced structures similar to those in a healthy pancreas.